WEBVTT

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Welcome.

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Today we're going to make diving
into the introduction to Black Parasites.

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Your speakers today are myself, doctor.

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Mark. Toria.

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I'm the medical director of parasitology
at Air European,

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a professor of pathology
at the University of Utah.

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Joining me is Blaine Matheson,

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an R&D scientist and parasitology
specialist therapy

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and an adjunct instructor in pathology
at the University of Utah.

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Our learning objectives for today

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are to understand the role of lab testing

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for the blood parasites
that we are going to discuss today.

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We're also going to recognize the major

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general blood parasites,
as they are quite diverse.

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And lastly, we're going to investigate
some of the clinical associations

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and the syndromes with some of these
major common blood parasites.

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So clinical parasitology
can involve many different organ systems.

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In a separate video,

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Blaine and I have actually covered
the major common

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parasites of brains skin, soft tissue,
lungs, liver and the GI. You.

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But today we're going to do exclusively

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those parasites that inflect
and infect the blood stream.

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So what?

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Parasite testing really falls
into one large catch all method.

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And that's that peripheral blood smear.

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So we'll start
with an overview of this method.

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And then rather than just go through
an exhaustive list of different methods

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as we introduce the different organisms,

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we'll talk about specific and nuanced,

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methods
that are used for those specific diseases,

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as there are quite specific situations,

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both timing of disease
and manifestation of disease,

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where the test you do
is going to be slightly different.

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So a traditional blood smear exam is done

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either by collecting peripheral
blood or a finger stick.

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And we

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take the
blood and we smear it onto a glass slide.

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That smear is then stained with either

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a game sustain or a right stain.

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Now there are some laboratories

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that use a third option,
which is a right games a stain.

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Typically, the right stain is preferred
by the hematology field.

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The King's A stain is preferred
by the parasitology field

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and the right games,
and it meets in the middle, and that

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it has a stain features of a right
which is more focused on the red blood

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cells, as well as the game
which is stain more,

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preferably to the parasite.

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Any parasitology lab
should be able to read

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and interpret
any of these types of stains.

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But in general, a game
that provides the best parasite

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stain retention and details
of different morphological features,

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some of which we'll talk about
as we enter, the different organisms.

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The thick

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smear is
intended for increasing our sensitivity.

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So on top here, you see a large
volume of blood that's spotted

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in the center of the slide
and allowed to dry

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over, extended period of time.

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This leads to license of the red cells

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and release of intracellular parasites

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onto a background
of essentially cell debris.

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This allows
for a more sensitive detection,

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but for some parasites,
it doesn't allow you to do full species.

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Level identification.

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Whereas the thin smear uses a less,

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amount of blood.

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But it also has a fixation step

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which creates intact red blood cells,

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which allows you to do, kind of a snapshot

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in time of what the parasites look like
in their native environment.

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So this is where we can identify
the species that's present.

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And it also allows us
to do a calculation of percent past Tamia,

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which we can do by counting the amount
of parasitized red blood cells, divided

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by the total number of red blood cells
and a defined field, number of fields.

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Now, the utility of the

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blood smear is very well established.

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This methods can use for many decades
for the detection of black parasites.

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General consensus
is that a flux managed to be performed

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every 6 to 8 hours,
at least three different times.

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In particular, if the first or the second,

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smear are negative
and there's a high clinical suspicion.

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So essentially a patient has signs
and symptoms

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and a travel exposure perform
the first blood smear.

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If that's negative
and symptoms are persisting.

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Perform
a second one six, eight hours later.

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And then again if that's negative,
another one six hours 6 to 8 hours later.

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So this puts us at about three
interrogations over a 24 hour period.

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But again,
depending on how that 6 or 8 hours

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is collected,
it can really span into a second day.

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On this slide here, what we're seeing
is a typical field, a field

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on the left of what Plasmodium falciparum
would look like in a thin smear.

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We can see the intact red blood cells.

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And on the right side we see Plasmodium
falciparum in a fixed me.

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And you see this kind of faint haze

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of cell debris
with the liberated parasites, amongst it.

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So the major blood parasites

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we're going to cover in this talk
can be broken down into the protozoa,

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which include some malaria
causing Plasmodium

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that Basia, the Trypanosoma,

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and then the helminths,
specifically the several nematodes,

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including the causative agents
of lymphatic filariasis.

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Local area in Brazil.

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Lower, lower and manzanilla.

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And lastly, we will include a short,

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shout out to the spirits.

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And this is not
because they are parasites, but

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because they can be incidentally

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found on a blood smear
in, interrogations, often

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when looking for something like malaria
with a cycling fever.

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Okay.

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So we're going to start with Plasmodium,
because it's

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probably the most common blood parasite
seen in most labs.

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And it's one of the most clinically relevant to accurately detect and identify.

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There's four primary

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species of what we call
human malaria, human plasmodium.

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And what we mean by

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that is that humans are the natural
intermediate host for the species.

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There's also about a dozen or so zoonotic
species.

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And Doctor
Kataria are going to go over those briefly

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with you
a little bit later of the lecture.

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But for now we're going to start off

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with the four primary human species,
which are Plasmodium falciparum,

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Plasmodium vivax, Plasmodium
valley and Plasmodium malaria.

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Now the symptoms of malaria
are kind of highly variable and often

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fairly nonspecific.

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Things like headache,
myalgia, arthralgia, weakness,

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GI distress, fever and chills.

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But one of the hallmarks of Plasmodium
is cyclic fever.

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Ng, which is

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where you get these fever spikes
tied to the rupturing of a sky isn't.

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And we'll go through the life
cycle in just a second.

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And then there's a lot of other less
common symptoms

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which can be can vary based on,

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the parasite Timea, the parasite load

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and also the preexisting condition
that the patient might have.

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So here's the plasmodium life cycle.

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And I think to it the plasmodium life
cycle is one parasite life cycle where

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I think it is very important to understand
definitely on the human side of things.

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So I'm going to walk you
through it, briefly, but also completely.

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So we'll start with infection,
where the mosquito injects

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the spore associate stage
while taking a blood meal.

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So spores sites are carried via
the bloodstream to the liver,

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where they infect the hepatocyte,
and they reproduce asexually,

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forming a hepatic or liver.

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Sky isn't,

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Marisela.

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It's released from the skies, isn't,
and get into the bloodstream.

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And this starts to a rather acidic cycle.

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Now, as many of you may know,
the parasites like Plasmodium

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vivax and Plasmodium

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obviously sequester in the liver
and can cause relapses later in life.

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That sequestration
happens upon initial infection only,

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back to the erythrocyte cycle.

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The reservoir white infected erythrocyte
and the earliest stage

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is called a ring form. Trophies. Zeolite.

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You sometimes hear that there's
four stages of Plasmodium ring trove.

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Computer science guys.

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Well, ring is just a really young
trophy site.

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And as the the trophy matures,
it takes one of two pathways.

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It either becomes a blood sky's on,
which perpetuates the acidic cycle.

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And as I mentioned earlier,
the rupture of the sky's on is timed is,

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timed as a fever spikes.

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The patient is experiencing
the other pathway can take as it can

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become a gamete, a site which is a dead
end stage in the human host.

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The whole purpose of the gamete,
a site, is to get picked up

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by the mosquito,
to initiate the sexual cycle,

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because the mosquito is actually
the definitive host.

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As humans, we're just kind of the
the lowly intermediate host here.

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We're just kind of it ends to a means,
but all the action actually goes in

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and goes on in the mosquito
and it goes through cycles.

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Oh, kindly formation and osis formation.

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Plasmodium is related to things
like Cryptosporidium, Cyclospora

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and Toxoplasma.

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So all they have the same life
cycle involving a sexual stage

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which results in oh, so, you know, cyst
containing infectious spores.

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Oh, it's

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the host

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eventually ruptures the spores or it's
make it to the, mouthparts of the mosquito

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to be injected in the next host
when taking the next blood meal.

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And the cycle continues.

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So I'm going to cover
the first two species of Plasmodium,

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and then Doctor
Kataria is going to cover the second two.

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So Plasmodium falciparum,
this is the most common.

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It's the most clinically relevant.

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And it's the species that biologically
could have the highest parasitism here.

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So identifying Plasmodium
falciparum is probably a top priority

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when it comes to malaria diagnosis,
especially here in the United States

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where you may not have adequate
travel history.

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So you don't know
what's coming in your lab.

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Most of the time
it is going to be Plasmodium falciparum.

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It's it is by far the most commonly seen,
at least in in imported cases

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in areas have their own, percentages
of what's more common.

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But in in countries where most of the
plasmodium detected is in travelers or,

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immigrants from other countries,

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Plasmodium falciparum is going to be
the most common species seen.

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It also has one of the widest
distributions of Plasmodium.

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Basically occurring circum tropical
around the world in the tropics

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and subtropics of Asia, Africa,
the Caribbean and Latin America.

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The fevers tend to cycle
every 24 to 48 hours,

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so it's the shortest
of the four human species.

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But if you have a really high
parasitic Mia, it can be almost continuous

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or feel like it's continuous.

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So some of the morphologic features
of falciparum,

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there's some kind of hallmark things
that you hear about,

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such as the thin, delicate cytoplasm,
the double chromatin dot,

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the appliqué form
and the multiple infected erythrocyte.

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These four features,
seen in the absence of other stages,

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is highly suspicious of falciparum,

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but it's important to know
that any species can have those.

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In other words, double dots
does not automatically mean falciparum

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a multiple infected erythrocyte
does not automatically mean falciparum.

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The two stages you're most likely going
to see in peripheral blood

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are the the ring form trophies, the whites
and the gamete a site.

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And that's because the later troves
and the sky's ons produce a

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an antigen that causes them

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to sequester in larger vessels,
rarely make it into the peripheral blood.

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Now, you can see them in peripheral blood,
but usually only

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when there's very high parasitic mas or

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or the patient has some kind of
underlying condition on the right there.

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You see,

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the banana shape could be the site
that's the most characteristic structure.

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There's there's no other stage
or species of human

00:12:42.316 --> 00:12:44.550
plasmodium
that's going to look anything like that.

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Here's some

00:12:46.400 --> 00:12:49.650
more kind of hallmark features
of Plasmodium falciparum.

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On the left center there.

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You've got the applique form right here
where it's

00:12:54.950 --> 00:12:57.083
kind of sitting on the periphery.

00:12:57.083 --> 00:12:59.816
In the center, you have
what's kind of called the headphone forms,

00:12:59.816 --> 00:13:03.016
where you have the kind of double
chromatin dot on the far right.

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You have a mouse clefts.

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These are these kind of chunky structures.

00:13:07.466 --> 00:13:11.266
There's many ways
analogous to the stippling of Plasmodium

00:13:11.266 --> 00:13:15.350
vivax and Plasmodium valley,
but they're not as commonly seen.

00:13:16.150 --> 00:13:21.116
A lot of it has to do with the collection
and the, the, the lot

00:13:21.116 --> 00:13:25.516
and of the themes that you're using,
but they're generally fewer

00:13:25.516 --> 00:13:29.366
than in numbers that are stippling
and they're larger.

00:13:29.366 --> 00:13:32.966
I like to use the chocolate chip
cookie analogy, where most clefs are like

00:13:32.966 --> 00:13:36.083
chocolate
chunks, larger and fewer number souvenirs.

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Stippling is like chocolate chips.

00:13:37.500 --> 00:13:39.983
There's more of them,
and they're smaller number,

00:13:42.016 --> 00:13:44.250
probably the next most common species
seen,

00:13:44.250 --> 00:13:47.483
at least here in the United States,
is Plasmodium vivax.

00:13:48.350 --> 00:13:52.550
This, this species is it's
the more temperate of the plasmodium.

00:13:53.100 --> 00:13:55.733
So it's going to be in more East Africa,

00:13:55.733 --> 00:13:59.750
temperate Asia, for example, Central
Asia, parts of the Middle East,

00:14:00.000 --> 00:14:05.283
like Afghanistan, Pakistan, the Indian
subcontinent, it's in Southeast Asia.

00:14:05.300 --> 00:14:08.066
It's the only species
on the Korean peninsula.

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And it occurs throughout a lot
of Latin America, from Mexico down to,

00:14:13.283 --> 00:14:15.716
central South America.

00:14:15.716 --> 00:14:18.616
The species has a predilection
for immature

00:14:18.616 --> 00:14:22.616
to throw sites, so infected erythrocytes
tend to be larger.

00:14:22.950 --> 00:14:25.516
But that's not a strict requirement.

00:14:25.516 --> 00:14:28.350
But generally, when you're reading a blood
film, the site, enlarge

00:14:28.350 --> 00:14:31.350
the sites.

00:14:31.433 --> 00:14:32.483
Can be a hallmark of either

00:14:32.483 --> 00:14:35.850
Plasmodium vivax or Plasmodium or valley.

00:14:36.766 --> 00:14:41.216
Fever cycles are about every 48 hours,
so a little bit longer than falciparum.

00:14:41.666 --> 00:14:44.933
And as I mentioned
earlier, Plasmodium vivax can

00:14:46.916 --> 00:14:50.216
sequestered in the liver upon
initial infection and reactivate months

00:14:50.216 --> 00:14:55.100
or even years later unless that liver
stage is treated properly.

00:14:55.400 --> 00:14:59.000
And Doctor Kothari will be going over
treatment a little bit later in the talk.

00:15:00.000 --> 00:15:03.916
So some of your hallmark features
of Plasmodium vivax is the ring form.

00:15:03.916 --> 00:15:06.300
Troughs tend to be larger and thicker,

00:15:06.300 --> 00:15:09.900
often with a single chromatin dot,
but may have more than one.

00:15:10.666 --> 00:15:12.116
Notice what's going on here in the middle.

00:15:12.116 --> 00:15:14.033
This is an a very Amboy trough.

00:15:14.033 --> 00:15:14.850
Resorts are known

00:15:14.850 --> 00:15:19.150
for their really kind of grossly me
boy traversing vivax is vivacious.

00:15:19.166 --> 00:15:20.566
It likes to go everywhere.

00:15:20.566 --> 00:15:23.900
Notice also how it's kind of
taking the form of the cells around it.

00:15:24.316 --> 00:15:28.400
Vivax and to some degree of valley change
the fluidity of the cell membrane,

00:15:28.800 --> 00:15:31.100
which make up more polymorphic.

00:15:31.100 --> 00:15:32.000
That's another reason

00:15:32.000 --> 00:15:35.400
why infected overthrow sites often
look large on a peripheral blood film.

00:15:35.666 --> 00:15:37.816
They kind of pancake out on the smear.

00:15:37.816 --> 00:15:41.000
So some of the enlargement is
because they're in younger erythrocytes,

00:15:41.000 --> 00:15:44.333
but some of it's also an optical
illusion of smear prep.

00:15:44.900 --> 00:15:50.066
And both the middle and the far right
photos show the Schaffner stippling again

00:15:50.066 --> 00:15:51.383
compared to the mouse clefts

00:15:51.383 --> 00:15:55.466
we saw with falciparum
much more numerous and much smaller.

00:15:56.550 --> 00:15:57.750
These next stage show the

00:15:57.750 --> 00:16:01.966
advanced, stage
seen in blood of vivax on the left gamete.

00:16:01.966 --> 00:16:04.516
A sites tend to be very large, very round.

00:16:04.516 --> 00:16:07.516
They take up most of the erythrocyte.

00:16:07.616 --> 00:16:08.600
I find the gamete.

00:16:08.600 --> 00:16:11.850
A site is probably the hardest stage
to separate from a valley.

00:16:12.300 --> 00:16:15.300
On the right
is the skies, on the right here.

00:16:15.766 --> 00:16:17.500
And the mature skies on

00:16:17.500 --> 00:16:20.500
is one of the best features
for separating vivax in a valley.

00:16:20.783 --> 00:16:24.233
This is a mature sky, is that you could
tell because the pigment has coalesced.

00:16:24.683 --> 00:16:28.800
And if you count them, a number of marzo
sites, there's greater than 15 to 20.

00:16:29.116 --> 00:16:32.900
Typically vivax
is going to have around 12 to 24.

00:16:33.300 --> 00:16:37.966
Oh Valley, which Doctor Couturier
will cover in a second has fewer 8 to 12.

00:16:37.966 --> 00:16:41.850
So if you have a mature sky,
isn't that's one of the best features for,

00:16:42.383 --> 00:16:46.400
morphologically separating Plasmodium
vivax and Plasmodium o Valley.

00:16:47.483 --> 00:16:49.800
So for both known animal valley

00:16:49.800 --> 00:16:53.033
well again
a lot of the same features with vivax

00:16:53.033 --> 00:16:58.416
where the preferential infection
of the immature red blood cells, but again

00:16:58.416 --> 00:17:02.183
not absolutely,
you know, 100% restricted by any means.

00:17:03.000 --> 00:17:05.966
But this does cause it to have lower
pristine years.

00:17:05.966 --> 00:17:09.316
And we consider that's
kind of the third most

00:17:09.650 --> 00:17:13.516
clinically encountered species,
after vivax.

00:17:14.083 --> 00:17:16.666
And it's a if you look

00:17:16.666 --> 00:17:20.700
at the map in the lower right,
you'll notice compared to Vivax

00:17:20.700 --> 00:17:24.416
and falciparum,
it's much more geographically constrained.

00:17:24.833 --> 00:17:28.550
So that that probably explains

00:17:28.550 --> 00:17:31.550
a bit of why it's not encountered as much.

00:17:32.400 --> 00:17:34.700
Again, shares the same fever

00:17:34.700 --> 00:17:37.700
cycle characteristics with vivax.

00:17:37.850 --> 00:17:41.216
And it has the same complication
of the left, liver phase.

00:17:41.216 --> 00:17:46.500
And so lights reactivating months to year
after primary infection.

00:17:47.416 --> 00:17:50.416
So something that's
that's a nice characteristic

00:17:50.916 --> 00:17:55.400
seen often with Plasmodium Valley
is this kind of

00:17:55.816 --> 00:18:01.333
elongating of the infected red cells
is sometimes called Amber nation.

00:18:02.833 --> 00:18:06.083
You know valley at the reward is oval.

00:18:06.533 --> 00:18:10.316
And that's kind of describes what
these cells kind of sometimes look like.

00:18:10.316 --> 00:18:13.316
They almost take an oval like morphology.

00:18:13.516 --> 00:18:16.166
In this field in the center, it's
see, it's kind of oval shape

00:18:16.166 --> 00:18:19.733
with these variations
coming off either end.

00:18:20.416 --> 00:18:23.416
And that's,
that's very typical for a valley.

00:18:23.666 --> 00:18:28.733
But you also have to be careful
if the, red cells all around

00:18:28.733 --> 00:18:32.550
it that are uninfected
are showing these types of, carnations

00:18:32.550 --> 00:18:36.833
or star like, protrusions,
the blood could be old.

00:18:37.216 --> 00:18:38.483
And so that can be an artifact.

00:18:38.483 --> 00:18:42.683
So these are things that you look
for as features, but you have to take it

00:18:42.683 --> 00:18:45.566
in the whole context.
What the picture showing you.

00:18:45.566 --> 00:18:48.116
If all the red cells look kind of weird,

00:18:48.116 --> 00:18:51.266
you can't fixate on these type of features
with a lot of confidence.

00:18:52.200 --> 00:18:55.850
Now, if you see a shies isn't with colors

00:18:55.850 --> 00:19:00.016
taking away a pigment
and 8 to 14 mirasol lights,

00:19:00.383 --> 00:19:03.383
now you're in a nice, supportive,

00:19:03.833 --> 00:19:06.566
structure for Plasmodium, a valley.

00:19:06.566 --> 00:19:10.100
However, if the pigment is not coalesced,

00:19:10.100 --> 00:19:13.433
essentially it's distributed
throughout the cell.

00:19:13.916 --> 00:19:17.366
You have to be very careful
to not overinterpret

00:19:17.366 --> 00:19:21.750
this such design as being a valley,
because it could still be an immature

00:19:22.216 --> 00:19:26.583
vivax tries on it,
just hasn't completely developed color.

00:19:26.600 --> 00:19:28.400
That's the pigment, and gotten

00:19:28.400 --> 00:19:31.400
the number of mirrors
or lights up to the normal range.

00:19:31.883 --> 00:19:35.116
So on this example, very similar
to what we saw with Plasmodium vivax,

00:19:36.466 --> 00:19:39.466
they shift their stippling as that more

00:19:39.716 --> 00:19:43.133
chocolate chip appearance multiple small
throughout the cell.

00:19:43.616 --> 00:19:46.133
Unlike vivax we have more of a,

00:19:46.133 --> 00:19:49.166
rounded to oval shaped, internal

00:19:50.333 --> 00:19:50.600
trough.

00:19:50.600 --> 00:19:53.600
So like they're not as like keep boy
looking and space filling.

00:19:54.500 --> 00:19:56.216
And you can see from radiation
on the cell as well.

00:19:56.216 --> 00:19:59.900
And same in the field on the right where
we have a lot of those same features,

00:20:00.800 --> 00:20:02.933
with the more, constrained,

00:20:02.933 --> 00:20:05.933
rounded or oval shape to give us a light.

00:20:06.150 --> 00:20:09.500
We've got the same region off the end
of the cell, and the Shifnal starts.

00:20:10.666 --> 00:20:11.850
Plasmodium malaria.

00:20:11.850 --> 00:20:14.850
The fourth of the human malaria is,

00:20:15.500 --> 00:20:18.500
this is again probably

00:20:18.866 --> 00:20:22.800
the least encountered for a few reasons.

00:20:23.066 --> 00:20:28.200
So Plasmodium malaria prefers
to infect the senescent red blood cells.

00:20:28.200 --> 00:20:32.483
So the older cells, the ones that are
close to turning over in the cell cycle.

00:20:33.016 --> 00:20:35.666
And so that that really constrains

00:20:35.666 --> 00:20:39.766
the type of of parasite team
is that it achieves because it's not,

00:20:41.566 --> 00:20:44.566
actively seeking out reticular sites.

00:20:45.383 --> 00:20:48.383
And you know, to select cells.

00:20:49.066 --> 00:20:54.200
The other thing with these infections is
they tend to be more often asymptomatic.

00:20:54.200 --> 00:20:57.866
Now that could be because
they're not infecting as many cells.

00:20:57.866 --> 00:21:01.650
And so your body is not,
being as negatively

00:21:02.116 --> 00:21:05.116
impacted
by the amount of red cell destruction.

00:21:05.866 --> 00:21:09.500
Again, also,
if the geographic distribution is,

00:21:10.516 --> 00:21:13.700
a little bit
less than falciparum and vivax,

00:21:13.700 --> 00:21:16.050
but it's still pretty, widespread.

00:21:16.050 --> 00:21:21.233
So this is probably more of an issue
of biology rather than the epidemiology.

00:21:21.450 --> 00:21:24.450
Also with this, the fevers
tend to be about every 72 hours,

00:21:24.950 --> 00:21:29.416
possibly, again represented by the fact
that they are, preferentially

00:21:29.416 --> 00:21:33.383
infecting the senescent red blood cells,
which are just fewer in the body.

00:21:34.250 --> 00:21:36.350
Some of the features
of malaria that are helpful,

00:21:37.733 --> 00:21:39.266
this shines

00:21:39.266 --> 00:21:42.650
on has what's called a rosette type
distribution.

00:21:42.650 --> 00:21:46.133
So the mirror is a lighter,
a little bit more dispersed

00:21:46.133 --> 00:21:49.650
around evenly throughout the cell
and call us pregnant.

00:21:49.650 --> 00:21:52.650
And then in the middle
to know that it's mature.

00:21:53.100 --> 00:21:56.100
That can be the sites that tend to be the

00:21:56.400 --> 00:21:59.400
kind of a smallest of

00:21:59.633 --> 00:22:03.533
the, plasmodium malaria, vivax
and or valley.

00:22:03.533 --> 00:22:05.850
And again, they don't look anything like
the banana shaped.

00:22:05.850 --> 00:22:08.116
Give me those types of off serum.

00:22:08.116 --> 00:22:09.716
You might see things like

00:22:09.716 --> 00:22:13.500
band form trophies or lights,
which is where the trough is.

00:22:13.500 --> 00:22:16.616
So it's just stretching
from one cell wall to another

00:22:16.883 --> 00:22:19.883
so that on both the left
and the right examples,

00:22:21.300 --> 00:22:23.850
another example that we sometimes see.

00:22:23.850 --> 00:22:24.950
But again, keep in mind

00:22:24.950 --> 00:22:27.950
a lot of these features are shared
between multiple species.

00:22:28.666 --> 00:22:33.566
This morphology, the bird's eye morphology
where the chromatin is actually looking

00:22:34.016 --> 00:22:36.683
like it's in the middle of the ring,

00:22:36.683 --> 00:22:39.683
as opposed to out
to the peripheral outside.

00:22:39.683 --> 00:22:42.983
And then these are, so-called basket forms

00:22:43.516 --> 00:22:46.200
where, it's basically just a space filling

00:22:46.200 --> 00:22:49.450
cytoplasm, within the trough.

00:22:49.516 --> 00:22:49.883
So light.

00:22:49.883 --> 00:22:55.433
But again, you can see this
with o Valley and vivax as well.

00:22:55.433 --> 00:22:59.266
So, you know,
if you take the whole picture of what

00:22:59.266 --> 00:23:03.216
you're seeing on the slide, that's how
you should make diagnosis, not by any one

00:23:03.383 --> 00:23:07.466
single feature that you might see
on one infected red blood cell.

00:23:08.566 --> 00:23:09.600
So a question that often

00:23:09.600 --> 00:23:13.100
comes out this
what about the other Plasmodium species.

00:23:13.766 --> 00:23:16.100
And this has become kind of a hot topic

00:23:16.100 --> 00:23:19.100
in the last 20 years with,

00:23:20.116 --> 00:23:22.733
the emergence or perhaps

00:23:22.733 --> 00:23:27.300
just recognition
of zoonotic Plasmodium infections

00:23:27.833 --> 00:23:34.283
and we want to talk about this because
we want to acknowledge its significance

00:23:34.833 --> 00:23:37.816
while also giving a word of warning

00:23:37.816 --> 00:23:40.816
against jumping
on the hyperbole of this subject.

00:23:41.783 --> 00:23:44.783
So what we're specifically talking
about are simian malaria.

00:23:45.266 --> 00:23:48.800
So these are malaria infections

00:23:49.200 --> 00:23:54.450
that are biologically found
in their natural host in monkeys.

00:23:55.100 --> 00:23:57.616
So when we talk about these infections

00:23:57.616 --> 00:24:00.316
in humans,
there are some notic infections there.

00:24:00.316 --> 00:24:03.650
A mosquito feeds off a primate.

00:24:04.316 --> 00:24:07.066
And then the cycle continues.

00:24:07.066 --> 00:24:10.200
And that mosquito net mosquito
then feeds on a human and transmits.

00:24:10.650 --> 00:24:16.516
So for this to happen you have to have
close proximity of primates to humans.

00:24:16.916 --> 00:24:19.733
So that really geographically restricts

00:24:19.733 --> 00:24:22.650
where these infections
can jump into humans.

00:24:22.650 --> 00:24:24.600
There is a anodic process.

00:24:24.600 --> 00:24:29.566
And when I say geographically restricted,
it's not just these countries

00:24:29.566 --> 00:24:33.050
or this region, but it's also, you know,

00:24:33.566 --> 00:24:36.566
is there a primate in the general vicinity

00:24:36.900 --> 00:24:40.550
of those humans
who are at risk for the mosquito bites?

00:24:41.033 --> 00:24:45.450
So it is a little bit more nuanced
than just are they in this country?

00:24:46.200 --> 00:24:49.966
So the biggest example is Plasmodium
Ngozi,

00:24:49.966 --> 00:24:53.000
which we'll talk about in more detail
in the coming slides.

00:24:53.866 --> 00:24:57.566
But if you look at this list, you know
that the take home message here is

00:24:58.883 --> 00:25:01.883
there are multiple simian in malaria

00:25:02.400 --> 00:25:06.150
that have been described
in any human infections.

00:25:06.683 --> 00:25:08.866
And they represent,

00:25:08.866 --> 00:25:10.316
you know,

00:25:10.316 --> 00:25:12.500
vast different parts of the world,

00:25:12.500 --> 00:25:15.083
probably through evolutionary processes

00:25:15.083 --> 00:25:17.816
that adapted to a specific primate host.

00:25:17.816 --> 00:25:20.816
And humans just happen to be encroaching
in that environment.

00:25:22.200 --> 00:25:25.166
You know, two at the bottom
that are fairly interesting ideas

00:25:25.166 --> 00:25:30.150
is Plasmodium simian in South America,
which there's some evidence that perhaps

00:25:30.566 --> 00:25:35.033
Plasmodium vivax
actually came across the ocean with humans

00:25:35.483 --> 00:25:39.466
and maybe jumped into monkey populations
in the New World.

00:25:39.916 --> 00:25:43.600
And the same hypothesis success
with Plasmodium, Brazilian

00:25:44.333 --> 00:25:48.166
on the perhaps
Plasmodium malaria came across with humans

00:25:48.750 --> 00:25:51.166
and then got introduced to the monkey

00:25:51.166 --> 00:25:54.316
population and evolved into a subspecies.

00:25:54.800 --> 00:25:57.266
That nomenclature
still not completely accepted,

00:25:57.266 --> 00:26:00.316
but it's an interesting
biological evolutionary idea.

00:26:03.050 --> 00:26:05.550
So a little bit more plasmodium ngozi.

00:26:05.550 --> 00:26:10.583
So again, a simian malaria
that has a very narrow

00:26:10.916 --> 00:26:14.750
geographic distribution
in specific parts of Southeast Asia.

00:26:15.200 --> 00:26:18.200
So I always warn when we'll talk about,
you know, we'll say

00:26:18.200 --> 00:26:21.916
they don't just say Southeast Asia because
it's really not all of Southeast Asia.

00:26:22.500 --> 00:26:25.100
It's a specific

00:26:25.100 --> 00:26:28.883
island region that encompasses
Malaysia and Indonesia

00:26:29.333 --> 00:26:32.333
is the majority of where cases
have been described.

00:26:32.366 --> 00:26:36.150
And that's not to say that
there aren't cases outside of there,

00:26:36.616 --> 00:26:40.616
but this is where the majority
of human cases have been described.

00:26:41.866 --> 00:26:44.900
And also here's an interesting one,
because it can

00:26:44.900 --> 00:26:48.166
mimic human
malaria species in different ways.

00:26:48.800 --> 00:26:53.750
So these infections tend to be fairly
severe in many cases.

00:26:54.150 --> 00:26:58.650
So that kind of mimics more the clinical
presentation of Plasmodium falciparum

00:27:00.016 --> 00:27:02.300
on the blood smear morphology.

00:27:02.300 --> 00:27:06.150
On the right here we see this band forms.

00:27:06.466 --> 00:27:09.000
And that can strand rings.

00:27:09.000 --> 00:27:10.550
So that kind of

00:27:10.550 --> 00:27:12.533
leads us back to that kind

00:27:12.533 --> 00:27:15.533
of looks a little bit
like Plasmodium malaria.

00:27:15.533 --> 00:27:19.966
And down below
we have a shies I would call us pregnant

00:27:20.450 --> 00:27:24.266
and this sort of elongated mirror
so they can actually look even more

00:27:24.766 --> 00:27:26.250
elongated than that.

00:27:26.250 --> 00:27:29.250
That's hallmark for Plasmodium
and we'll see.

00:27:29.416 --> 00:27:33.950
But if they don't have that nice clear
elongation,

00:27:34.400 --> 00:27:37.400
they can be mistaken for malaria as well.

00:27:37.883 --> 00:27:40.666
In the early infection,

00:27:40.666 --> 00:27:44.983
the slides tend to all be rings,
so they do look more like the septum.

00:27:45.466 --> 00:27:50.116
But as the infection progresses
and they're steamy, it goes up.

00:27:50.450 --> 00:27:54.500
We start to see more
as the features of malaria might work.

00:27:54.500 --> 00:27:58.700
Being consistent stepparents
Tamia often can reach, you know,

00:27:58.700 --> 00:28:02.700
five plus percent, which we typically
don't see with Plasmodium malaria,

00:28:03.800 --> 00:28:04.666
and then

00:28:04.666 --> 00:28:07.666
Nucleic Acid Amplification Testing or Nat

00:28:07.766 --> 00:28:10.466
can be performed for malaria.

00:28:10.466 --> 00:28:12.900
We'll talk about that
in the next couple slides.

00:28:12.900 --> 00:28:16.316
And if the test has not been carefully
designed,

00:28:17.266 --> 00:28:22.466
it could actually cause
a cross-reactive signal on the Nat test,

00:28:22.800 --> 00:28:25.800
which would identify it
as Plasmodium vivax.

00:28:26.300 --> 00:28:27.750
And then just a final over.

00:28:27.750 --> 00:28:30.750
Note of caution for

00:28:31.200 --> 00:28:33.116
trying to make an identification
of Plasmodium.

00:28:33.116 --> 00:28:35.566
You'll see.

00:28:35.566 --> 00:28:38.216
We want to make sure that people
just don't default and don't see it,

00:28:38.216 --> 00:28:42.716
because it's the new chic thing
to try to report a case of nosy.

00:28:43.133 --> 00:28:47.700
These are exceedingly rare, you know,
you should really be coming in

00:28:47.700 --> 00:28:50.783
to a blood smear,
looking for common things, being common,

00:28:51.533 --> 00:28:54.716
and then follow your good practices
that you've learned.

00:28:55.316 --> 00:28:57.600
Evaluate the morphology objectively.

00:28:57.600 --> 00:28:59.600
Follow your mental flowchart.

00:28:59.600 --> 00:29:02.600
Are the cells normal, static,
or macro acidic?

00:29:02.700 --> 00:29:05.700
What do the trapezoids look like?

00:29:05.933 --> 00:29:08.400
What are the schisms look like?
If they're present?

00:29:08.400 --> 00:29:10.850
What typical media sites look like,

00:29:10.850 --> 00:29:13.300
then yes, everything together.

00:29:13.300 --> 00:29:14.216
It just looks weird.

00:29:15.383 --> 00:29:17.333
Then you can consider

00:29:17.333 --> 00:29:20.333
another species
like Plasmodium animals at that point.

00:29:20.400 --> 00:29:23.866
But the first thing you want to do,
if you start to see those type of odd

00:29:23.866 --> 00:29:28.966
features, is confirm that the patient
has the geographic exposure

00:29:28.966 --> 00:29:33.016
that would actually be relevant
for something like Penalosa.

00:29:34.166 --> 00:29:37.166
And then a final step, maybe

00:29:37.433 --> 00:29:40.433
to consider doing a nucleic acid
amplification test.

00:29:40.500 --> 00:29:43.583
If there is one
that specifically can detect

00:29:43.950 --> 00:29:46.883
Plasmodium, those.

00:29:46.883 --> 00:29:48.500
Now for treatment,

00:29:48.500 --> 00:29:51.016
this is going to depend
on a lot of nuances.

00:29:51.016 --> 00:29:53.100
And and really

00:29:53.100 --> 00:29:56.100
for treatment in most cases

00:29:56.333 --> 00:29:59.333
consulting with experts
is is always recommended.

00:29:59.866 --> 00:30:03.300
So things that have to be looked
at how severe the disease,

00:30:03.650 --> 00:30:06.750
what species is infecting,
where was it acquired

00:30:07.200 --> 00:30:10.200
geographically as a patient you.

00:30:10.733 --> 00:30:12.000
Antimalarials.

00:30:12.000 --> 00:30:15.083
Especially during the time they thought
they were thought to have acquired it,

00:30:15.616 --> 00:30:19.016
because that can give you some guidance
on what you may or may not want to use.

00:30:20.400 --> 00:30:20.850
So we do

00:30:20.850 --> 00:30:24.600
have resistance issues with Plasmodium

00:30:24.600 --> 00:30:27.616
falciparum
and to some extent Plasmodium vivax.

00:30:28.400 --> 00:30:30.600
Specifically with the drug chloroquine.

00:30:30.600 --> 00:30:33.900
So there's a link included in this
talk to the CDC

00:30:34.433 --> 00:30:36.800
that goes through all the treatment
algorithms.

00:30:36.800 --> 00:30:38.600
It's beyond the scope of this talk.

00:30:38.600 --> 00:30:42.750
But that would be a resource that as a
training physician, you'd want to consult.

00:30:43.200 --> 00:30:46.950
Or if a physician contacts
the lab asking questions about,

00:30:47.400 --> 00:30:50.183
you know, treatment,
you want to really point them

00:30:50.183 --> 00:30:53.600
to that and recommend,
consult with infectious disease.

00:30:54.566 --> 00:30:57.000
So if you have

00:30:57.000 --> 00:30:59.850
occasion who diagnosed with cancer

00:30:59.850 --> 00:31:02.266
or vivax and their exposure

00:31:02.266 --> 00:31:06.800
region is such that there's no documented
chloroquine resistance,

00:31:07.366 --> 00:31:10.583
chloroquine is the recommended
first line drug.

00:31:11.400 --> 00:31:14.100
If the patient is returning from an area

00:31:14.100 --> 00:31:18.800
that does have chloroquine resistance,
then there's a stepwise

00:31:18.800 --> 00:31:22.916
process of different options,
and those are shown below 1234

00:31:24.200 --> 00:31:26.566
for different treat treatment approaches.

00:31:26.566 --> 00:31:29.566
And then as as we mentioned
earlier in the talk,

00:31:29.700 --> 00:31:33.383
if you're suspecting or you've diagnosed

00:31:33.766 --> 00:31:36.766
Plasmodium vivax and Laurel Valley,

00:31:37.516 --> 00:31:41.966
then there is an additional drug
you want to give to treat those,

00:31:42.650 --> 00:31:45.050
liver face. If there's a whites

00:31:45.050 --> 00:31:48.150
that can be to fennekin
or primarily phosphate.

00:31:49.733 --> 00:31:53.633
And then I mentioned that we would talk
about other methods on the blood smear.

00:31:54.083 --> 00:31:58.950
So two methods that have gained traction
in the last decade for malaria

00:31:58.950 --> 00:32:02.033
diagnosis are nucleic acid amplification

00:32:02.033 --> 00:32:05.033
tests and antigen detection assays.

00:32:05.416 --> 00:32:09.166
So for detecting Plasmodium
antigen from blood in the United States

00:32:09.166 --> 00:32:14.366
especially, we'll focus on
just the one FDA cleared rapid car test.

00:32:14.783 --> 00:32:17.033
What's the binaxnow malaria.

00:32:17.033 --> 00:32:20.033
Now this test is a

00:32:20.150 --> 00:32:23.900
really of most benefit for hospitals.

00:32:23.900 --> 00:32:26.850
You can't do a blood smear on site
and do it quickly.

00:32:26.850 --> 00:32:30.800
So this can get you a result
in less than 30 minutes,

00:32:31.433 --> 00:32:35.300
which can tell you either
Plasmodium falciparum or,

00:32:37.050 --> 00:32:40.050
another yellow Plasmodium species

00:32:41.366 --> 00:32:44.666
other than falciparum,
or including possible and

00:32:46.166 --> 00:32:50.850
these tests are rapid, but
they're not as sensitive as a blood smear.

00:32:51.350 --> 00:32:54.766
So whether the test is positive
or negative,

00:32:55.283 --> 00:32:58.800
you still have to get a blood
smear to back it up.

00:32:58.800 --> 00:33:02.533
One to confirm the species by blood smear,

00:33:02.566 --> 00:33:05.866
regardless of what the card says, and two,
if it's negative,

00:33:06.383 --> 00:33:09.950
you may detect a low pass
to me, a specimen by blood smear.

00:33:10.883 --> 00:33:13.883
And so if we look at the,

00:33:14.633 --> 00:33:16.616
the characteristics of this test,

00:33:16.616 --> 00:33:19.050
it's been designed to be most sensitive

00:33:19.050 --> 00:33:21.800
for Plasmodium falciparum because again,

00:33:21.800 --> 00:33:25.100
that's the most widespread
and the most clinically significant.

00:33:25.816 --> 00:33:29.066
But it can detect the other three

00:33:29.066 --> 00:33:32.700
human species as well, albeit
with less sensitivity.

00:33:33.383 --> 00:33:38.333
And then some data and studies have shown
that some of these simian malaria species

00:33:38.783 --> 00:33:42.566
can also be detected
with these rapid antigens,

00:33:43.016 --> 00:33:46.500
but with even less sensitivity
than with the human species.

00:33:47.183 --> 00:33:49.966
So if we look at this table to the right,

00:33:50.933 --> 00:33:53.516
these parasitic levels are reported in

00:33:53.516 --> 00:33:56.566
kind of the international standard,
not the US standard.

00:33:56.566 --> 00:33:59.866
In the US, we typically report
in percent purest genius.

00:34:00.416 --> 00:34:02.966
So A55 thousand

00:34:02.966 --> 00:34:06.116
parasites per ML,
which would be our second line down

00:34:06.116 --> 00:34:10.950
approximately is equivalent to our .12
5% tenia,

00:34:11.516 --> 00:34:14.516
which puts us at about 99%

00:34:14.683 --> 00:34:17.333
sensitivity for Plasmodium falciparum,

00:34:17.333 --> 00:34:20.633
which is actually pretty good
for Plasmodium vivax.

00:34:21.166 --> 00:34:24.166
That drops down more to about 90%.

00:34:24.766 --> 00:34:27.266
So not bad by any means, but definitely

00:34:27.266 --> 00:34:30.266
not at the same level as a blood smear.

00:34:30.433 --> 00:34:33.116
Now not test for malaria at this point.

00:34:33.116 --> 00:34:36.116
These are not the standard of care
for diagnosis.

00:34:36.716 --> 00:34:40.966
If they're primarily available
as laboratory developed tests only

00:34:40.966 --> 00:34:42.800
at specific

00:34:42.800 --> 00:34:46.816
public health or reference labs,
and the specificity and sensitivity,

00:34:47.183 --> 00:34:50.450
assuming the tests have been
well designed are both excellent.

00:34:51.050 --> 00:34:53.366
And these can be useful
in different scenarios.

00:34:53.366 --> 00:34:57.983
So say you have a suspected
mixed infection and the epidemiology

00:34:58.116 --> 00:35:03.000
support that this can be helpful
for trying to detect that in an athlete.

00:35:03.000 --> 00:35:04.050
It does a multiplexed

00:35:05.266 --> 00:35:07.516
detection and reporting.

00:35:07.516 --> 00:35:10.516
If you have a specimen
that's got a really low pass, steamy,

00:35:11.150 --> 00:35:13.166
so scenario, say

00:35:13.166 --> 00:35:16.316
if there's organisms on any of the slides,
then you look at,

00:35:17.750 --> 00:35:21.866
well, you're pretty confident it's
Plasmodium can help you get the species

00:35:22.350 --> 00:35:24.866
or you have a very few minor

00:35:24.866 --> 00:35:27.533
organisms
and you're pretty sure it's Plasmodium.

00:35:27.533 --> 00:35:32.250
But you can't rule out the PCR, especially
if there's an ambiguous travel history.

00:35:32.750 --> 00:35:35.300
It can be helpful for that purpose.

00:35:35.300 --> 00:35:38.966
And then if the test actually has
a specific target for Plasmodium, normally

00:35:39.650 --> 00:35:41.866
that's a good way
to do a rule in rule out,

00:35:41.866 --> 00:35:44.783
especially if you have a weird looking
smear.

00:35:44.783 --> 00:35:49.100
One of the limitations of these tests is
that they're not quantitative pcrs right

00:35:49.100 --> 00:35:52.816
now, for the tests that are available
in most labs and United States.

00:35:53.266 --> 00:35:55.250
So even if you did

00:35:56.400 --> 00:35:59.716
a PCR such not as your primary detection,

00:36:00.116 --> 00:36:03.116
you still have to do a smear to do.

00:36:05.033 --> 00:36:06.316
Next we're going to cover,

00:36:06.316 --> 00:36:10.133
babesiosis,
caused by parasites in the genus genus.

00:36:10.150 --> 00:36:15.916
But this is probably the second
most common, blood parasite seen,

00:36:15.983 --> 00:36:19.316
especially here in the United States,
where we have some endemic species.

00:36:20.600 --> 00:36:23.683
The most common species, in humans

00:36:23.683 --> 00:36:27.383
are probably in the northeast
of the US of North America.

00:36:27.433 --> 00:36:29.683
ABC McCrary and in the Old world.

00:36:29.683 --> 00:36:34.616
But Busia Duncan I which are both
transmitted by ticks in the genus Ixodes,

00:36:35.033 --> 00:36:36.233
but some other species

00:36:36.233 --> 00:36:39.983
are transmitted by other ticks for now,
it's believed that Duncan I in the West

00:36:40.366 --> 00:36:44.850
is actually transmitted by a derma center,
but most of the cases in the U.S.

00:36:44.850 --> 00:36:49.400
are going to be Busia, McCrory,
which is transmitted by Ixodes,

00:36:49.400 --> 00:36:53.550
primarily Ixodes scapular, as all
babies are considered zoonotic.

00:36:53.866 --> 00:36:56.366
And we'll look at the life
cycle in just the sex. So,

00:36:59.216 --> 00:37:03.350
the, the, the
zoonotic potential is really unlimited.

00:37:03.350 --> 00:37:06.716
And as I think as we encroach
more on nature and more into the habitats

00:37:06.716 --> 00:37:11.066
of the natural hosts, we're going to see
more and more novel babesiosis popping up.

00:37:11.066 --> 00:37:12.766
And every now and then they do.

00:37:12.766 --> 00:37:15.800
You know, when I was at the CDC,
we had a case from Tennessee, for example,

00:37:15.800 --> 00:37:18.916
and I think there's been
a couple recent cases out of Texas. So,

00:37:20.033 --> 00:37:23.866
the the zoonotic potential is
really unknown because we just don't know

00:37:23.866 --> 00:37:27.383
what's out there
and what humans might be exposed to.

00:37:28.100 --> 00:37:30.350
So here's the life cycle of bbca.

00:37:30.350 --> 00:37:33.750
The the large cycle on the right
is actually the tick life cycle.

00:37:33.983 --> 00:37:38.033
We're going to focus here on the Beasley
and McCrory with cycles between,

00:37:38.716 --> 00:37:41.250
rodents, such as deer mice

00:37:41.250 --> 00:37:44.516
and the scapula as tick.

00:37:44.866 --> 00:37:46.650
Now, the deer is important to maintain

00:37:46.650 --> 00:37:50.066
the tick life cycle,
but not important for the busy life cycle.

00:37:50.600 --> 00:37:55.366
The life cycle of the busy in humans
is actually not quite fully understood.

00:37:55.700 --> 00:37:58.250
The problem is
it is not as morphologically

00:37:58.250 --> 00:38:00.233
differentiated as Plasmodium.

00:38:00.233 --> 00:38:02.116
So when you see rings on a blood film,

00:38:02.116 --> 00:38:04.400
it could be a gamete,
it could be a trophies. Right.

00:38:05.716 --> 00:38:09.050
It's generally believed that while humans
can get for Busia,

00:38:09.050 --> 00:38:13.066
Weir and Cape were incapable of giving it
to a tick to give back to a rodent.

00:38:13.466 --> 00:38:15.533
That hasn't been definitively proven yet.

00:38:15.533 --> 00:38:21.350
But, a lot of authorities consider a kind
of a dead end zoonotic disease in humans.

00:38:22.066 --> 00:38:25.066
We do get it from the bite of the tick.

00:38:25.950 --> 00:38:27.166
Stages seen in humans.

00:38:27.166 --> 00:38:29.183
Again,
we don't really differentiate the stages

00:38:29.183 --> 00:38:32.183
because most of them
are not morphologically differentiated.

00:38:32.516 --> 00:38:35.183
You might have seen that classic Maltese
cross formation.

00:38:35.183 --> 00:38:38.416
You can kind of see it down here
in the lower left.

00:38:38.816 --> 00:38:41.333
That's the those are Morozov. Right.

00:38:41.333 --> 00:38:44.333
So this is kind of analogous to the sky on

00:38:45.500 --> 00:38:47.400
in Plasmodium because that's

00:38:47.400 --> 00:38:50.416
where your asexual reproduction
in the throw sites going to occur.

00:38:52.283 --> 00:38:53.933
So symptoms are highly variable.

00:38:53.933 --> 00:38:57.300
That could often be asymptomatic,
especially in young healthy people

00:38:57.300 --> 00:39:01.650
that like to enjoy the outdoors who are a
great demographic for getting the disease

00:39:01.650 --> 00:39:04.916
because of increased risk of tick tick
exposure.

00:39:05.516 --> 00:39:07.166
Symptoms are pretty nondescript.

00:39:07.166 --> 00:39:11.716
You know, your typical stuff like fevers,
chills, sweating, myalgia, fatigue,

00:39:13.366 --> 00:39:15.200
hemolytic anemia is possible.

00:39:15.200 --> 00:39:18.200
You see this more frequently with BCR,

00:39:21.300 --> 00:39:23.300
divergence in the old world,

00:39:23.300 --> 00:39:26.300
where you,
where you see the symptoms most severe,

00:39:26.300 --> 00:39:29.216
at least here in North America, are people
who are immunocompromised,

00:39:29.216 --> 00:39:32.116
such as people that are elderly and people
that are splenic.

00:39:32.116 --> 00:39:35.116
Those are kind of your two hallmark,

00:39:35.116 --> 00:39:38.033
groups
that suffer from higher parasitic mas

00:39:38.033 --> 00:39:41.300
and more severe clinical presentation.

00:39:41.850 --> 00:39:46.433
Diagnosis is pretty much done
exclusively by blood film examination

00:39:46.850 --> 00:39:49.550
because of the lack of morphologic,
well defined

00:39:49.550 --> 00:39:52.550
morphologic features
and morphologic variability.

00:39:52.700 --> 00:39:56.850
We don't typically
we can't identify species morphologically

00:39:56.850 --> 00:39:59.866
and we typically don't diagnose stages
either.

00:39:59.866 --> 00:40:01.650
So whereas on a Plasmodium report, A

00:40:01.650 --> 00:40:05.350
may say something like Plasmodium
falciparum rings and cometo

00:40:05.400 --> 00:40:09.383
sites of a reported
probably just say saber a species.

00:40:09.900 --> 00:40:14.150
There are serologic and molecular tests
available, but they're not routinely used.

00:40:14.866 --> 00:40:18.266
They're not commonly used for routine
clinical diagnosis.

00:40:18.500 --> 00:40:23.300
They can be very helpful in trace back
investigations, for example, say in blood

00:40:23.300 --> 00:40:28.200
transfusion associated cases of Berbizier,
which is becoming less common now that,

00:40:29.216 --> 00:40:32.216
now that the blood supply has a

00:40:32.516 --> 00:40:35.516
as an not for screening.

00:40:36.383 --> 00:40:37.966
So but morphology there's

00:40:37.966 --> 00:40:40.966
several hallmark things are Baeza
one of them is extreme

00:40:41.216 --> 00:40:45.750
morphic variation
and in the rings or in the parasite.

00:40:45.750 --> 00:40:48.950
Well, we'll say parasite because we really
don't know what all these stages are.

00:40:49.250 --> 00:40:53.550
If you look at the slide here on the far
right, notice how some are really tiny,

00:40:53.700 --> 00:40:57.266
some are big,
some are in chains, some are in pairs.

00:40:57.600 --> 00:41:00.600
This high variability
is a hallmark of the bezier

00:41:00.900 --> 00:41:03.866
on a slide of, say, plasmodium falciparum.

00:41:03.866 --> 00:41:07.350
Most of your rings are going to be fairly
uniform in size and shape in relation

00:41:07.350 --> 00:41:08.250
to one another.

00:41:08.250 --> 00:41:10.766
But but it can be highly variable.

00:41:10.766 --> 00:41:13.016
It's also, often vaccinated.

00:41:13.016 --> 00:41:15.316
So you might see a white center.

00:41:15.316 --> 00:41:19.050
But busy does not produce
hemos own pigment which Plasmodium does.

00:41:19.050 --> 00:41:22.950
So presence of pigment rules
out the Busia on the far right.

00:41:22.950 --> 00:41:26.333
Here you've got the that classic Maltese
cross formation.

00:41:26.633 --> 00:41:29.633
Great for board reviews,
bad for clinical practice.

00:41:29.850 --> 00:41:33.983
I have very rarely seen, Maltese
cross on a blood film.

00:41:33.983 --> 00:41:37.550
And, you know, in nearly
25 years of doing clinical parasitology

00:41:38.033 --> 00:41:39.900
and in the middle see this cluster here.

00:41:39.900 --> 00:41:42.016
These are extracellular forms.

00:41:42.016 --> 00:41:45.383
But Busia has what we call true
extracellular forms.

00:41:45.750 --> 00:41:48.233
And one must be careful
not to confuse those with things.

00:41:48.233 --> 00:41:51.000
For example, like, clusters of platelets.

00:41:53.100 --> 00:41:53.300
It's the

00:41:53.300 --> 00:41:56.633
last person we'll talk about
are the Trypanosoma.

00:41:57.166 --> 00:42:00.150
And there's two human

00:42:00.150 --> 00:42:03.150
pathogenic Trypanosoma
the where and I focus on

00:42:03.316 --> 00:42:06.533
those are Spanish amakhosi
which is the causative

00:42:06.533 --> 00:42:11.616
agent of chocolate disease
in the New World and depends on the sea

00:42:12.166 --> 00:42:15.416
which causes African sleeping
sickness in the Old World.

00:42:15.416 --> 00:42:17.300
In Africa,

00:42:17.300 --> 00:42:20.266
these look similar

00:42:20.266 --> 00:42:22.800
at first glance, but actually

00:42:22.800 --> 00:42:25.800
on a blood smear can be distinguished,

00:42:26.216 --> 00:42:29.966
by the morphological size of their
can item last,

00:42:30.050 --> 00:42:33.050
which is this posterior located,

00:42:34.733 --> 00:42:38.933
nuclear DNA containing structure on

00:42:40.166 --> 00:42:41.366
Trypanosoma persi.

00:42:41.366 --> 00:42:44.366
It's much smaller kind of nondescript

00:42:44.416 --> 00:42:47.416
and on cruzi it's big and bold.

00:42:48.000 --> 00:42:50.150
So starch patterns on the cruzi.

00:42:50.150 --> 00:42:52.166
So this is

00:42:52.166 --> 00:42:54.150
I feel like it's gotten more

00:42:54.150 --> 00:42:58.216
mainstream awareness
because it it's very easy

00:42:58.216 --> 00:43:01.433
to sensationalize and,
and, and make dramatic about

00:43:02.600 --> 00:43:04.916
the way you get this. So

00:43:04.916 --> 00:43:07.616
the tri dormant bug,
which is the kissing bug

00:43:07.616 --> 00:43:10.616
is the factor for dependance
on the cruzi high.

00:43:10.850 --> 00:43:15.383
And what happens is these bugs at night
come out of the shadows

00:43:15.383 --> 00:43:19.400
and the cracks of walls and ceilings
and very rudimentary housing,

00:43:20.266 --> 00:43:22.966
particularly like thatched roofs and rats.

00:43:22.966 --> 00:43:26.666
And they take blood meal
on the human host,

00:43:27.450 --> 00:43:30.766
and then they defecate
as soon as they finish their blood meal,

00:43:31.400 --> 00:43:34.400
which happens as the human
actually itches or,

00:43:34.616 --> 00:43:38.350
or, you know, just puts a hand to the,
to the wound, say,

00:43:38.900 --> 00:43:41.550
and aids
and inoculating it into the wound.

00:43:41.550 --> 00:43:44.033
It's possible
the feces to go directly into the wound.

00:43:44.033 --> 00:43:48.116
But often these despite become actually
so the human can facilitate this as well.

00:43:49.216 --> 00:43:50.416
The symptoms

00:43:50.416 --> 00:43:54.150
in the acute phase,
many patients are actually symptomatic.

00:43:55.050 --> 00:43:58.050
If they have a lesion at the

00:43:58.250 --> 00:44:00.750
the bite site, that's called a coma.

00:44:00.750 --> 00:44:03.600
And that can be a pretty dramatic
skin lesion.

00:44:03.600 --> 00:44:07.216
And then another clinical manifestations
cut the on your sign.

00:44:07.766 --> 00:44:10.616
And this is kind of a a swelling

00:44:10.616 --> 00:44:13.316
around the eye or around the mouth.

00:44:13.316 --> 00:44:15.566
Typically proximal to where the bite

00:44:15.566 --> 00:44:18.566
of the, kissing bug is.

00:44:19.100 --> 00:44:22.883
This may or may not have a fever and body
aches and malaise associated with it.

00:44:23.516 --> 00:44:26.666
And very rarely do you get cardiac

00:44:26.666 --> 00:44:29.800
or CNS involvement in these kid infections
with Japan.

00:44:29.816 --> 00:44:32.783
As a courtesy, I.

00:44:32.783 --> 00:44:34.950
Again, the life cycle on the right

00:44:34.950 --> 00:44:39.300
we see the tritium and bug having,

00:44:40.283 --> 00:44:42.616
having mascots replicating in the met.

00:44:42.616 --> 00:44:47.600
Got those go into the trip
amassed goats in the hind got.

00:44:47.600 --> 00:44:50.633
And then upon taking the blood
meal, they get defecated out.

00:44:51.866 --> 00:44:54.866
Those then go to,

00:44:55.133 --> 00:44:57.566
various tissues in the body

00:44:57.566 --> 00:45:00.150
replicate becoming mast goats

00:45:00.150 --> 00:45:03.150
and then this cycle,

00:45:03.383 --> 00:45:05.666
can basically

00:45:05.666 --> 00:45:06.416
become lytic.

00:45:06.416 --> 00:45:10.133
They get in the bloodstream
and then get taken out by a new host

00:45:10.133 --> 00:45:14.000
when the, the kissing bug feeds again.

00:45:14.450 --> 00:45:17.450
Now, there are other mammalian,

00:45:18.983 --> 00:45:21.983
species that can act as intermediates.

00:45:22.350 --> 00:45:24.950
It doesn't just have to be a human.

00:45:24.950 --> 00:45:27.950
Really, if you're warm blooded and,

00:45:28.500 --> 00:45:31.250
in second feed off you,
you can have a potential for service

00:45:31.250 --> 00:45:35.633
in the air
as a host so tremendous in some accrues

00:45:35.633 --> 00:45:40.466
in a chronic phase,
can cause very severe manifestations.

00:45:40.466 --> 00:45:43.733
So the two most common
that are worried about

00:45:43.733 --> 00:45:48.016
are the cardiac involvement
or gastrointestinal tract involvement.

00:45:49.616 --> 00:45:52.616
Approximately 70 or 80%

00:45:52.816 --> 00:45:57.900
of people infected with tick resi
chronically are asymptomatic

00:45:57.900 --> 00:46:00.900
for their entire life,
and this is termed the indeterminate form.

00:46:01.650 --> 00:46:05.250
This is where they may be seropositive
by actually serology,

00:46:05.666 --> 00:46:11.066
but develop no further symptoms,
and then 20 or 30% of patients

00:46:11.416 --> 00:46:15.616
will progress to an active form
disease called the determinate form.

00:46:16.200 --> 00:46:19.783
And this can manifest
as things like medical

00:46:19.800 --> 00:46:24.233
and cardiomyopathy,
often fatal, and mega esophagus.

00:46:25.550 --> 00:46:26.900
So the diagnosis of

00:46:26.900 --> 00:46:30.116
Trypanosoma cruzi
has a bit complicated in the acute phase.

00:46:30.916 --> 00:46:33.150
Microscopy is primarily

00:46:33.150 --> 00:46:37.316
done on blood CSF
if appropriate, to symptoms

00:46:37.950 --> 00:46:40.616
or biopsy at the,

00:46:40.616 --> 00:46:44.483
bite site or proximal to the bite site
could also take a PCR

00:46:45.000 --> 00:46:48.000
if available at a specialized laboratory,

00:46:48.083 --> 00:46:51.666
and you can even do culture,
to try to detect it.

00:46:52.066 --> 00:46:55.283
Microscopy is by a by and large,
the most commonly used

00:46:55.966 --> 00:46:58.966
diagnostic for acute phase.

00:46:59.750 --> 00:47:01.400
Now for chronic phase

00:47:01.400 --> 00:47:04.316
serology is really your only option.

00:47:04.316 --> 00:47:06.983
So I g antibodies

00:47:06.983 --> 00:47:09.983
are the most utilized and reliable.

00:47:10.016 --> 00:47:14.866
But even still it's recommended
to use two different IGT tests

00:47:15.416 --> 00:47:18.416
to try to optimize accuracy
to confirm diagnosis.

00:47:19.500 --> 00:47:21.616
The treatment of T cruzi

00:47:21.616 --> 00:47:24.616
is best in the acute phase

00:47:25.066 --> 00:47:29.000
in the chronic phase,
sometimes it's to far beyond treatable.

00:47:29.000 --> 00:47:29.666
At that point,

00:47:30.866 --> 00:47:31.766
there's an FDA cleared

00:47:31.766 --> 00:47:34.766
drug called bentonite as well.

00:47:34.766 --> 00:47:38.900
And then there's an investigational drug
which you can only obtain from the CDC,

00:47:39.500 --> 00:47:41.716
which is not here to MOX.

00:47:41.716 --> 00:47:45.866
Now, the asking spread
surmise surmises, is Trypanosoma II.

00:47:46.500 --> 00:47:50.666
This is affected by the positive fly
or the closson, a genus of flies.

00:47:51.766 --> 00:47:53.900
Humans are the main reservoir for this.

00:47:53.900 --> 00:47:54.383
They're.

00:47:54.383 --> 00:47:57.450
It can be maintained
and catalysts are sorry

00:47:57.916 --> 00:48:00.650
and cattle's as a reservoir.

00:48:00.650 --> 00:48:03.650
We generally try to think about humans
as being,

00:48:03.983 --> 00:48:06.600
the main key in the life cycle.

00:48:06.600 --> 00:48:10.516
So similar to T cruzi II,

00:48:10.966 --> 00:48:13.966
all the replication exists

00:48:14.400 --> 00:48:16.400
in the insect vector.

00:48:16.400 --> 00:48:19.400
And then when the GC flight takes a blood
meal,

00:48:19.700 --> 00:48:24.000
it actually injects
the triple mascot in the blood meal.

00:48:24.000 --> 00:48:26.850
So this is not a defecation
process. This is a,

00:48:28.616 --> 00:48:28.950
through the

00:48:28.950 --> 00:48:32.116
blood meal oral, excretion process.

00:48:32.783 --> 00:48:37.316
And then with the drip and pasta
coats, they

00:48:37.316 --> 00:48:41.866
then transform in the bloodstream,
and then they multiply.

00:48:42.233 --> 00:48:45.766
And so we typically find these in fluids
like blood

00:48:46.316 --> 00:48:48.650
lymphatic fluid and spinal fluid.

00:48:48.650 --> 00:48:52.200
If it progresses to that phase
and again the

00:48:52.533 --> 00:48:56.766
the DC fly will take it up
from circulating, trip

00:48:56.800 --> 00:48:59.800
a mascot's in the blood
and the cycle continues.

00:49:00.533 --> 00:49:02.700
So early phases of t

00:49:02.700 --> 00:49:08.183
persi include skin ulcers
and that associates with the, bites

00:49:08.183 --> 00:49:13.966
side of the city fly, often accompanied
by a fever and lymphatic, reactivity.

00:49:13.966 --> 00:49:17.116
So you'll have enlarged lymph nodes
proximal to the bite

00:49:18.316 --> 00:49:21.233
later stage.

00:49:21.233 --> 00:49:24.233
You can get kind of a symptom free and,

00:49:24.283 --> 00:49:25.166
a phase.

00:49:25.166 --> 00:49:28.433
It's kind of like nothing's
really happening clinically, but

00:49:29.150 --> 00:49:30.233
rather physiologically.

00:49:30.233 --> 00:49:32.000
There's, you know, further,

00:49:33.833 --> 00:49:34.766
maturation of the

00:49:34.766 --> 00:49:37.950
infectious process throughout the body
and that this,

00:49:38.116 --> 00:49:42.566
this duration can be very short
or it can be quite prolonged.

00:49:43.016 --> 00:49:46.550
And then late end stage,
this is where you have to kind of

00:49:46.550 --> 00:49:50.150
some the lessons to coma and death
that we typically see,

00:49:50.933 --> 00:49:53.750
in patients in Africa
who have not been treated.

00:49:53.750 --> 00:49:56.750
So the Trypanosoma procedure
has two subspecies.

00:49:57.083 --> 00:50:00.116
Now by microscopy
we can't tell these apart.

00:50:00.116 --> 00:50:03.116
That can be determined
only by molecular testing.

00:50:03.166 --> 00:50:07.216
And the two species are Japan

00:50:07.216 --> 00:50:11.033
that's on the Pacific
and the NC and Japan is on a per se.

00:50:11.033 --> 00:50:14.033
I wrote NC, so gamma NC

00:50:14.483 --> 00:50:18.750
is kind of a west fraction of Africa
in this map below.

00:50:19.316 --> 00:50:22.550
And so the way I remember
this is in the U.S, you gamble out

00:50:22.550 --> 00:50:27.533
west in Vegas and then Rhodesia
or the Rhodesian region of Africa.

00:50:27.900 --> 00:50:30.266
It's kind of in eastern Africa.

00:50:30.266 --> 00:50:32.366
And Rhode Island is in the eastern part
of the United States.

00:50:32.366 --> 00:50:35.366
So gamble, Rhode Island,

00:50:35.516 --> 00:50:38.516
two ways
you can kind of remember those subspecies.

00:50:40.316 --> 00:50:43.100
Now, why is it important to know those?

00:50:43.100 --> 00:50:45.766
So Canby NC tends to have lower pairs.

00:50:45.766 --> 00:50:48.683
Seniors, less severe disease.

00:50:48.683 --> 00:50:51.050
It's less apt to get to the CNS.

00:50:51.050 --> 00:50:54.050
And if it does get to the CNS,
typically it takes years to get there.

00:50:54.416 --> 00:50:58.400
Now Roady NC on the other hand,
has higher pers tenia, so it's

00:50:58.400 --> 00:51:02.450
actually easier to check in the blood,
much more severe clinical presentation,

00:51:03.616 --> 00:51:06.833
much more tropic to CNS, tissues.

00:51:07.350 --> 00:51:10.350
And it takes typically less
than three quarters of a year

00:51:10.800 --> 00:51:13.700
to progress to CNS involvement.

00:51:13.700 --> 00:51:17.600
The diagnosis is a little more
straightforward than with TR cruzi.

00:51:18.166 --> 00:51:23.633
So in the acute phase we have microscopy
and you can do this from blood lymph node

00:51:23.633 --> 00:51:27.716
aspirates shank or fluid at the bite site
or bone marrow.

00:51:28.166 --> 00:51:33.683
In the chronic phase you're typically
thinking at the sleeping sickness level.

00:51:33.683 --> 00:51:35.600
So existing microscopy of the CSF

00:51:36.566 --> 00:51:39.566
treatment

00:51:39.800 --> 00:51:40.466
really depends on

00:51:40.466 --> 00:51:43.466
the subspecies and the source,

00:51:43.916 --> 00:51:46.650
where it is in the body. So

00:51:46.650 --> 00:51:48.150
for Rodi NC,

00:51:48.150 --> 00:51:50.866
if it's in the blood or lymphatic says

00:51:50.866 --> 00:51:53.900
serum in, it's the drug for the CNS phase.

00:51:54.300 --> 00:51:56.816
It's similar persol

00:51:56.816 --> 00:51:58.666
for BNC

00:51:58.666 --> 00:52:02.250
for the blood
lymphatic stage, it's contaminating

00:52:02.750 --> 00:52:05.750
and for the CNS is it's a floor thing.

00:52:06.450 --> 00:52:10.883
And the last group of parasites
we'll cover before this, the, Borelli

00:52:10.883 --> 00:52:15.416
Aspire kits are the floral nematodes,
the agents of filariasis.

00:52:15.416 --> 00:52:20.000
And these this these broadly,
these clinical conditions

00:52:20.000 --> 00:52:24.000
are caused by a group of nematodes
that are called the malarial nematodes.

00:52:24.500 --> 00:52:26.550
And on the right
we have the lower, lower life cycle.

00:52:26.550 --> 00:52:27.600
Just for this example.

00:52:27.600 --> 00:52:30.600
They all kind of
follow the same basic life cycle pattern.

00:52:30.750 --> 00:52:34.966
So we're not going to go over with every
with every genus and every disease.

00:52:35.366 --> 00:52:40.133
But they're all vector borne and they all
cycle between the human definitive host

00:52:40.616 --> 00:52:44.933
and a some kind of bloodsucking fly
intermediate host and vector.

00:52:45.500 --> 00:52:46.850
And so

00:52:46.850 --> 00:52:50.933
just to cover the lifecycle, briefly,
adults reside in somewhere on the body.

00:52:50.933 --> 00:52:55.083
And and you can see here on the left
we'll agrarian brood year.

00:52:55.100 --> 00:52:58.350
Typically
the lymphatic tissue low is in the skin.

00:52:58.650 --> 00:53:01.250
The eye manifestation is actually ectopic.

00:53:01.250 --> 00:53:05.866
And manzanilla is typically in
the mesenteric connective tissue in skin.

00:53:06.566 --> 00:53:08.283
And after mating the female.

00:53:08.283 --> 00:53:11.516
They don't lay eggs like a lot of the
nematodes deliver the intestinal tract.

00:53:11.516 --> 00:53:13.700
They they release micro area.

00:53:13.700 --> 00:53:17.966
Which of these really early first stage
larvae and they circulate in the blood.

00:53:17.966 --> 00:53:20.300
We're going to focus on the blood species
here.

00:53:20.300 --> 00:53:23.816
They circulate in the blood at the
optimal time when the vector is feeding.

00:53:24.350 --> 00:53:24.950
And then

00:53:25.916 --> 00:53:27.950
so they're picked up.

00:53:27.950 --> 00:53:29.866
They're are picked up
by an appropriate vector.

00:53:29.866 --> 00:53:33.016
When it's taking a blood meal,
they molt twice to become

00:53:33.016 --> 00:53:37.283
the infectious L3 larva,
and then they migrate to the proboscis.

00:53:37.283 --> 00:53:41.266
And when that vector takes a blood
meal, it's pass on to the next host.

00:53:41.266 --> 00:53:45.000
So, pretty direct cycle, human definitive

00:53:45.166 --> 00:53:48.266
host blood
sucking fly vector, intermediate host.

00:53:48.683 --> 00:53:52.166
I'll talk about the nuances of each
as we cover each of the diseases.

00:53:52.816 --> 00:53:56.150
Diagnosis of all of these
is pretty much made exclusively

00:53:56.150 --> 00:53:59.150
by the detection of the microflora
and blood films.

00:53:59.716 --> 00:54:03.016
There are serologic assays
for lymphatic filariasis,

00:54:03.016 --> 00:54:07.066
and there are some and again detection
assays for some of these as well.

00:54:07.316 --> 00:54:08.600
But they're not used,

00:54:08.600 --> 00:54:11.966
for routine clinical diagnosis,
at least not here in North America.

00:54:12.650 --> 00:54:16.283
So the first of these we're going
to start off with is lymphatic filariasis,

00:54:16.650 --> 00:54:19.650
which is caused by Wukari Bancroft de

00:54:19.816 --> 00:54:23.166
Bruges, Melia Imbruglia, Tomori, Wukari.

00:54:23.216 --> 00:54:27.500
Bancroft is basically a circle and
tropical in the tropics and subtropics.

00:54:27.500 --> 00:54:31.050
So tropical Africa, Southeast
Asia, the Pacific Islands,

00:54:31.366 --> 00:54:33.500
Caribbean and Latin America.

00:54:33.500 --> 00:54:37.700
Bruja Malai is is Central Asia
like the Indian subcontinent,

00:54:38.150 --> 00:54:42.150
South and East to Southeast Asia
and the Pacific Islands, and bruja

00:54:42.150 --> 00:54:47.100
to Moray is endemic to a few islands
in the lesser, soon soon to archipelago.

00:54:47.450 --> 00:54:49.400
They're all vectored by various
mosquitoes.

00:54:49.400 --> 00:54:52.500
Different genera
and species of mosquito transmit the worms

00:54:52.816 --> 00:54:55.816
depending on geographic location.

00:54:55.916 --> 00:54:59.933
The clinical presentation,
as the name suggests, is, lymphadenopathy.

00:54:59.933 --> 00:55:03.766
So, a lot of people like to think
of elephantiasis with these disease,

00:55:03.766 --> 00:55:06.766
which is the really exaggerated
lymphadenopathy, where you have this

00:55:07.050 --> 00:55:10.850
massive, edema build up in the lower
extremities, resulting

00:55:10.850 --> 00:55:16.166
in enlargement of the legs,
the groin, in men, the testes.

00:55:16.516 --> 00:55:20.716
This is really only seen in people
who grew up in endemic areas,

00:55:20.716 --> 00:55:23.700
and they've been constantly exposed over
a lot of their life.

00:55:23.700 --> 00:55:25.850
Casual visitors doing demic areas.

00:55:26.816 --> 00:55:27.616
Should not present

00:55:27.616 --> 00:55:30.616
with with classic elephantiasis.

00:55:31.516 --> 00:55:34.666
Diagnosis is made
by the finding of microflora in blood.

00:55:34.666 --> 00:55:36.566
They have a nocturnal periodicity,

00:55:36.566 --> 00:55:39.683
which means that the microflora
are mainly circulating at night.

00:55:39.983 --> 00:55:42.150
So you want to draw your blood
between 10 p.m.

00:55:42.150 --> 00:55:43.516
and 2 a.m..

00:55:43.516 --> 00:55:46.516
There is serology available
for these as well.

00:55:46.733 --> 00:55:50.450
Treatment varies depending on where
the disease was required

00:55:50.450 --> 00:55:53.950
and what other, floral nematodes
they might be infected with.

00:55:53.966 --> 00:55:56.966
DC is the drug of choice
for this organism,

00:55:57.300 --> 00:56:00.500
but if you have a mixed infection
with Anca, circa

00:56:00.950 --> 00:56:03.950
or lower,
you need to rethink your treatment.

00:56:04.316 --> 00:56:08.150
Because, DC is indicated in Anca circa

00:56:08.450 --> 00:56:12.116
and it's contraindicated in lowa
above a certain microfilm arrhythmia.

00:56:12.500 --> 00:56:16.200
So if, for example, you acquire
lymphatic filariasis in West Africa,

00:56:16.200 --> 00:56:19.433
where all of these occur and
you need to rule out the other species,

00:56:19.766 --> 00:56:22.733
and if you have lower,
you need to do a microfilm arrhythmia.

00:56:25.200 --> 00:56:27.800
Speaking of lowa, that's the next one
we're going to cover.

00:56:27.800 --> 00:56:30.750
It's caused by lower
low of the African eye worm.

00:56:30.750 --> 00:56:33.716
It is endemic to west central Africa.

00:56:33.716 --> 00:56:37.133
The associated with the association
with the eye is actually ectopic.

00:56:37.133 --> 00:56:40.166
These these are migrating adults
that end up in the eye.

00:56:40.166 --> 00:56:44.750
They typically live in the skin
where they cause a clinical presentation

00:56:44.750 --> 00:56:49.200
called Calabar swellings, which are soft,
palpable nodules on the skin.

00:56:49.650 --> 00:56:53.366
These are vectored by deer flies
and these have a diurnal periodicity

00:56:53.366 --> 00:56:56.116
because deer flies feed during the day.

00:56:56.116 --> 00:57:00.033
So if you suspect lowa, you want to
collect your blood between 10 a.m.

00:57:00.033 --> 00:57:02.450
and 2 p.m.

00:57:02.450 --> 00:57:04.966
and like with lymphatic filariasis,
diagnosis

00:57:04.966 --> 00:57:07.966
is made by finding the microfilm in blood.

00:57:08.033 --> 00:57:10.766
Or, if you're really lucky,
an adult pluck from the eye.

00:57:11.966 --> 00:57:15.650
The treatment is DSC, but only at lower

00:57:17.550 --> 00:57:19.516
ciliary mch levels.

00:57:19.516 --> 00:57:23.633
When you have a lower case,
you should do a microfilm premia. And,

00:57:24.750 --> 00:57:28.950
if it's below 8000 per milliliter,
you could trigger a DSC.

00:57:28.950 --> 00:57:32.000
If it's higher, you want to treat
without bend dissolve first.

00:57:32.000 --> 00:57:33.533
The lower the word burden.

00:57:33.533 --> 00:57:36.533
Prior to DSC administration,

00:57:36.716 --> 00:57:39.316
the last group we're going to talk about
associated with the blood

00:57:39.316 --> 00:57:41.033
are the mount snows.

00:57:41.033 --> 00:57:42.450
There's three species.

00:57:42.450 --> 00:57:44.033
Two of them are in blood.

00:57:44.033 --> 00:57:46.150
We're not really going
to talk about much about,

00:57:46.150 --> 00:57:49.516
menthol is stripped acerca,
which is a skin parasite in Africa.

00:57:49.916 --> 00:57:52.516
But the two you're likely to see in
blood are going to be bound.

00:57:52.516 --> 00:57:55.166
A person's which is native to Africa.

00:57:55.166 --> 00:57:58.883
But it's been introduced to Latin America,
including the Caribbean,

00:57:59.183 --> 00:58:00.600
and then Manzanillo SRT,

00:58:00.600 --> 00:58:03.666
which is naturally endemic
to Latin America and the Caribbean.

00:58:04.283 --> 00:58:08.400
These are transmitted by biting midges,
although black flies can also transmit

00:58:08.400 --> 00:58:12.900
Manzanillo SRT, they don't have a
they don't have a periodicity.

00:58:12.900 --> 00:58:15.650
So you can kind of find these in blood
at any time.

00:58:15.650 --> 00:58:17.033
I don't think anyone actually goes

00:58:17.033 --> 00:58:20.066
into a clinic
and a doc actually suspects manzanilla.

00:58:20.416 --> 00:58:21.200
They're usually found,

00:58:21.200 --> 00:58:24.616
incidentally, when blood is drawn
for other things, for example, malaria.

00:58:25.050 --> 00:58:28.316
Several of the manzanilla persons cases
I've seen in my career

00:58:28.550 --> 00:58:32.100
have actually been infected
with Plasmodium falciparum from Africa.

00:58:33.233 --> 00:58:33.900
There really are no

00:58:33.900 --> 00:58:37.466
treatment standards,
although DSC with diesel has been used.

00:58:37.666 --> 00:58:39.866
Also, ivermectin.

00:58:39.866 --> 00:58:42.866
These are your smallest in the micro area.

00:58:43.433 --> 00:58:46.433
They'll always lack a sheath and

00:58:48.000 --> 00:58:49.733
probably less commonly seen in

00:58:49.733 --> 00:58:52.733
clinical practice.

00:58:53.150 --> 00:58:55.583
And finally is our outlier.

00:58:55.583 --> 00:58:58.583
So again these are not parasites.

00:58:58.700 --> 00:59:02.116
But you can encounter them
on a blood smear, as you see in this image

00:59:02.116 --> 00:59:03.466
in the bottom right.

00:59:03.466 --> 00:59:06.900
This is a Borrelia in the relapsing fever
group

00:59:07.366 --> 00:59:10.366
of Borrelia in a peripheral blood smear.

00:59:11.183 --> 00:59:13.950
So when we're talking about

00:59:13.950 --> 00:59:17.333
Borrelia it's natural
to want to think Lyme disease.

00:59:17.900 --> 00:59:20.566
But there's actually two large

00:59:20.566 --> 00:59:23.566
conceptual groups of Borrelia.

00:59:23.716 --> 00:59:28.100
There's the line Borrelia that causes Lyme
disease in line like illness.

00:59:28.916 --> 00:59:31.366
And there's the relapsing fever group,

00:59:31.366 --> 00:59:34.133
which causes, as the name suggests,

00:59:34.133 --> 00:59:36.766
a fever that goes through a period

00:59:36.766 --> 00:59:41.000
stop, periodic lapse and spike. So

00:59:42.200 --> 00:59:43.233
what is often

00:59:43.233 --> 00:59:46.850
happen in our lab is
a patient is getting worked up for malaria

00:59:47.483 --> 00:59:50.483
because they have these fevers
that have come

00:59:50.566 --> 00:59:53.333
every, you know, 5 to 7 days.

00:59:53.333 --> 00:59:55.950
And maybe they have a concomitant

00:59:55.950 --> 00:59:58.950
travel history that would make sense
for malaria exposure.

00:59:59.250 --> 01:00:03.116
And then we look at the blood smear
and there's no malaria but there Sparky's.

01:00:03.916 --> 01:00:06.900
So the way that this works

01:00:06.900 --> 01:00:11.716
is if you get picked by a soft tick
carrying a relapsing fever,

01:00:11.716 --> 01:00:15.233
probably a species, you know, about a week
where nothing happens,

01:00:16.200 --> 01:00:18.050
that's your incubation phase.

01:00:18.050 --> 01:00:20.416
And you have about

01:00:20.416 --> 01:00:23.416
three days of symptomatic

01:00:23.566 --> 01:00:26.566
relapsing fever episodes,

01:00:26.850 --> 01:00:29.850
so that this happens three times
over the course of about a month.

01:00:30.450 --> 01:00:35.783
But in between each episode,
you have a seven day, a several period,

01:00:36.166 --> 01:00:39.900
and then a three day episode, seven day,
a febrile third episode.

01:00:40.466 --> 01:00:44.666
So that cycle isn't really consistent
with how malaria

01:00:45.300 --> 01:00:49.050
will present, but you can see how it
can be confused potentially.

01:00:51.416 --> 01:00:54.416
The symptoms that go along with this fever

01:00:54.566 --> 01:00:59.116
include headache, malaise,
myalgia, chills and nausea.

01:00:59.550 --> 01:01:02.550
And these chills and these

01:01:02.783 --> 01:01:05.666
headaches can be pretty severe.

01:01:05.666 --> 01:01:09.766
Like you can cause delusion, hysteria.

01:01:11.333 --> 01:01:14.566
Shaking chills
that are so bad that people are actually,

01:01:14.750 --> 01:01:18.533
like, experiencing muscle pulls and back
spasms.

01:01:18.950 --> 01:01:22.066
It's a pretty severe clinical presentation
with fevers

01:01:22.066 --> 01:01:25.066
that flash up to 105 Fahrenheit.

01:01:25.133 --> 01:01:28.133
And then when they come down from
that is when a lot of these,

01:01:28.583 --> 01:01:31.650
these neurological manifestations
like confusion

01:01:31.650 --> 01:01:34.650
and delirium happen,

01:01:34.650 --> 01:01:37.016
less frequently, arthralgia and vomiting.

01:01:37.016 --> 01:01:39.683
And then even less frequently,
these manifestations like

01:01:39.683 --> 01:01:42.683
G.I ocular and,

01:01:43.216 --> 01:01:46.216
and respiratory symptoms.

01:01:47.366 --> 01:01:50.033
So we diagnose these again

01:01:50.033 --> 01:01:52.650
by blood smear, often incidentally,

01:01:52.650 --> 01:01:55.583
by not just the richest
and most sensitive.

01:01:55.583 --> 01:01:58.433
And then in a patient
who's gone through their one

01:01:58.433 --> 01:02:02.216
month of symptoms
and then it's kind of an afterthought.

01:02:02.550 --> 01:02:06.766
Serology can be used to try to establish
a retrospective diagnosis.

01:02:07.550 --> 01:02:10.816
And a treatment
for all of these is doxycycline,

01:02:10.816 --> 01:02:15.116
which has been shown to be effective
and rapidly clear.

01:02:15.683 --> 01:02:18.466
The organism and say all symptoms

01:02:19.800 --> 01:02:22.050
now their geographic range.

01:02:22.050 --> 01:02:25.050
This is very you approximate

01:02:25.850 --> 01:02:28.850
but you can see Borrelia herms the eye
and the greenish

01:02:29.033 --> 01:02:33.600
shade encompasses most of the mountain,
West and Pacific mountains in the U.S.

01:02:33.600 --> 01:02:35.300
and Canada.

01:02:35.300 --> 01:02:39.000
Papalia Park lies about to be more
the southwest, especially the,

01:02:39.683 --> 01:02:42.866
the mountainous regions of the southwest
and lower elevations,

01:02:43.583 --> 01:02:46.316
and forms the eye tends to be
at the higher elevations.

01:02:46.316 --> 01:02:49.583
And then Brian Turcotte tends
to be kind of scattered

01:02:49.966 --> 01:02:53.483
in parts of Texas, the Ozarks
and the panhandle of Florida.

01:02:53.850 --> 01:02:56.850
Again, these ranges
are not perfectly established.

01:02:57.350 --> 01:03:00.000
It's very possible
that they're more broad than this.

01:03:00.000 --> 01:03:03.000
But this is kind of
where surveillance data has pointed us.

01:03:04.216 --> 01:03:07.316
So in summary, some of the high key points

01:03:07.966 --> 01:03:11.000
to remember
for the blood parasites, for malaria,

01:03:11.000 --> 01:03:14.900
they're all vector by Anopheles
mosquitoes, Plasmodium falciparum.

01:03:15.316 --> 01:03:18.316
That's our most dangerous
and most widespread.

01:03:18.466 --> 01:03:21.683
And we have to worry about
chloroquine resistance for vivax

01:03:22.166 --> 01:03:26.666
liver phase reactivation
and chloroquine resistance for evali

01:03:27.316 --> 01:03:30.316
the liver phase reactivation for malaria.

01:03:30.683 --> 01:03:31.466
Think about this one.

01:03:31.466 --> 01:03:34.516
Is the more mild
asymptomatic type of malaria

01:03:35.750 --> 01:03:36.950
for Propecia,

01:03:36.950 --> 01:03:39.750
this is a tick borne disease
in the genus Ixodes.

01:03:39.750 --> 01:03:42.750
In the United States,
especially for the most part

01:03:43.100 --> 01:03:45.450
highest risk in Hispanic patients

01:03:45.450 --> 01:03:48.450
or unable to filter the parasite
out of the blood.

01:03:48.900 --> 01:03:52.650
Frenchmen is I'm crazy, I
this is the causative agent of Chagas

01:03:52.650 --> 01:03:56.416
disease in the Americas
can lead to a chronic illness,

01:03:56.866 --> 01:03:59.516
which can cause both gastrointestinal

01:03:59.516 --> 01:04:02.516
and heart complications, including death

01:04:03.383 --> 01:04:05.300
threats. Depends on the person I.

01:04:05.300 --> 01:04:08.216
This is the cause of agent of African
sleeping sickness,

01:04:08.216 --> 01:04:12.000
which we primarily diagnose
through blood microscopy at all phases.

01:04:12.650 --> 01:04:15.050
And, it's

01:04:15.050 --> 01:04:18.833
mostly fatal if it progresses to the sun.

01:04:18.833 --> 01:04:21.650
The lessons phase

01:04:21.650 --> 01:04:23.333
for filariasis

01:04:23.333 --> 01:04:26.033
ae area causes lymphatic filariasis,

01:04:26.033 --> 01:04:29.483
and an extreme
chronic exposure is elephantiasis.

01:04:30.300 --> 01:04:32.966
La la la la. Causes.

01:04:32.966 --> 01:04:36.616
Calabar swellings
is the skin manifestation and is known

01:04:36.616 --> 01:04:39.616
as the African eye worm, where you can

01:04:39.616 --> 01:04:42.616
rarely find it and topically in the eye.

01:04:42.716 --> 01:04:43.616
Manzanilla.

01:04:43.616 --> 01:04:47.266
And as plain mentioned,
these are kind of incidental,

01:04:48.600 --> 01:04:50.266
celestial nematodes.

01:04:50.266 --> 01:04:53.150
They find typically
when you're looking for something else.

01:04:53.150 --> 01:04:57.166
And then lastly, as we just discussed, the
tick borne relapsing fevers, barricades

01:04:57.716 --> 01:05:01.650
which are affected by soft ticks,
have a widespread distribution

01:05:01.650 --> 01:05:04.650
across much of the western part
of North America,

01:05:04.766 --> 01:05:08.066
as well as other parts of the world,
and cause a cycling fever,

01:05:08.483 --> 01:05:11.483
which superficially can be mistaken
for malaria.

01:05:12.950 --> 01:05:13.950
And with that,

01:05:13.950 --> 01:05:17.900
we thank you for your time and attention
and encourage you.

01:05:18.166 --> 01:05:21.983
If you haven't seen the
get a companion lecture to this

01:05:22.250 --> 01:05:26.966
on the other organ systems for parasites
to please empower yourself to,

01:05:27.600 --> 01:05:30.650
familiarize yourself with that lecture
content to get a nice

01:05:31.200 --> 01:05:34.283
comprehensive
overview of parasitology and humans.

01:05:34.883 --> 01:05:35.683
Thank you so much.