Transcript MALARIA

“The awkward fact with which US policy wrestles is that
People flee the world’s Haitis for a combination of motives.
All are deserving of some compassion but how much?”
Newsweek, Dec. 4 1991
“Give me your tired, your poor,
Your huddled masses yearning to breathe free,
The wretched refuse of your teeming shore.
Send these, the homeless, tempest-tossed, to me”
Inscribed at base of Statue of Liberty, by Emma Lazarus
As you know
in the developing world treatable
infectious diseases remain big killers
Leading causes of death in Sub-Saharan Africa, South Asia, and Southeast Asia for persons age
0-44 (World Health Organization)
Now it’s time to look at number 3:
Malaria
Leading causes of death in Sub-Saharan Africa, South Asia, and Southeast Asia for persons age
0-44 (World Health Organization)
That’s right:
300 million new cases per year
making it the most prevalent serious
infectious disease!
Leading causes of death in Sub-Saharan Africa, South Asia, and Southeast Asia for persons age
0-44 (World Health Organization)
–2.1 billion people live in MALARIOUS areas
–Like HIV and TB, malaria is
–unequally distributed, even in the tropics
–In areas of Africa with high transmission
–there are 2700 deaths per day = 2 per minute
www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf
It’s especially hard on kids
It’s especially hard on kids
75% of the deaths are among African children
www.uhhg.org/mcrh/resources/video/malariappt.pdf
What Is malaria?

A mosquito-borne infectious disease caused by
Protozoan parasites of the genus Plasmodium
What Is malaria?

Transmitted only by Anopheles Mosquitoes
(>60 species!)
Seattle Biomedical Research Institute
What Is malaria?

The Disease can be Acute or Chronic
Acute Symptoms

Classical features include cyclic symptoms
– Cold stage: chills and shaking
– Hot stage:
children
fever, headache, vomiting, seizures in
– Sweating stage: weakness
– Feel well for period of time, then cycle repeats itself
www.uhhg.org/mcrh/resources/video/malariappt.pdf
In fact it is several different diseases
www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf
Each disease has a distinct course
Each disease has a distinct course
“Tertian Malaria”
(P.falciparum, P.ovale and P.vivax)
fever occurs every third day.
“Quartan Malaria”
(P. malariae)
fever occurs every fourth day.
www.uhhg.org/mcrh/resources/video/malariappt.pdf
Each disease has a distinct course
P.ovale and P.vivax
can cause chronic malaria,
reappearing after months or years
due to latent parasites in liver
www.uhhg.org/mcrh/resources/video/malariappt.pdf
Each disease also has a distinct
geographical distribution
www.uhhg.org/mcrh/resources/video/malariappt.pdf
Each disease also has a distinct
geographical distribution
www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf
Each disease also has a distinct
geographical distribution
www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf
Malaria damages the body
in a number of ways

Red blood cell destruction -> anemia

Waves of parasites bursting red blood cells
Lead to classic cycles of fever and chills
Malaria damages the body
in a number of ways

Changes adhesive properties of infected
Red blood cells -> blocking blood vessels
leading to Tissue hypoxia
Malaria damages the body
in a number of ways

If this happens in brain it is cerebral malaria
which is often fatal
Blocking blood
vessels can also
cause kidney failure
Malaria damages the body
in a number of ways
In severe cases 20% of patients can die,
even with the best care
DIAGNOSIS

Gold standard:
Multiple thick and thin
smears
Malaria is not currently a
serious threat in the US
 1300
cases in US per year
 Essentially all “imported”
 Also transfusion related malaria
www.uhhg.org/mcrh/resources/video/malariappt.pdf
Although….
www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf
Malaria is not currently a
serious threat in the US
However, this was not always
the case
Not that long ago….
www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf
It could come back!
www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf
Let step back and look
at the parasites that cause malaria
It was discovered
more than 100 years ago
A French army doctor in
Algeria observed
parasites inside red blood
cells of malaria patients
and proposed for the first
time that a protozoan
caused disease
Charles Louis Alphonse Laveran
www.uhhg.org/mcrh/resources/video/malariappt.pdf
1907 Nobel Prize for Physiology
or Medicine!
French army doctor in
Algeria observed
parasites inside red blood
cells of malaria patients
and proposed for the first
time that a protozoan
caused disease
Charles Louis Alphonse Laveran
www.uhhg.org/mcrh/resources/video/malariappt.pdf
So just who
is this
Plasmodium?
www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf
It’s not a
bacterium or
virus but a
eukaryote
like us
www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf
However,
unlike us
it lives a
solitary life
as a single
cell
www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf
Let’s go back to the family tree
Let’s go back to the family tree
http://drnelson.utmem.edu/Woods.Hole/slide5.png
Let’s go back to the family tree
You and me
http://drnelson.utmem.edu/Woods.Hole/slide5.png
mushrooms
You and me
http://drnelson.utmem.edu/Woods.Hole/slide5.png
mushrooms
You and me
plants
http://drnelson.utmem.edu/Woods.Hole/slide5.png
We are family….
mushrooms
You and me
Plasmodium
plants
http://drnelson.utmem.edu/Woods.Hole/slide5.png
They are on the same region of
the eukaryote tree as plants
You and me
Plasmodium
plants
http://drnelson.utmem.edu/Woods.Hole/slide5.png
Consistent with this,
we now know Plasmodium
and its relatives have a
remnant of the chloroplast
called the apicoplast
which may help it digest
heme and other things
it harvests from red blood cells
Consistent with this,
we now know Plasmodium
and its relatives have a
remnant of the chloroplast
called the apicoplast
which may help it digest
heme and other things
It harvests from red blood cells
We don’t have this sort of organelle
How might we use that fact??!
Plasmodium and its relatives
also have a specialized
Structure at one end of the cell
Involved in invading other cells
www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf
Plasmodium’s closer relatives
Include parasites causing
Babesiosis, Toxoplasmosis,
And Cryptosporidiosis
Plasmodium has a wildly complex life cycle
6
2
5
3
4
1
Purves et al., Life: The Science of Biology, 4th Edition
And that’s just in the mosquito!
6
2
5
3
4
1
Purves et al., Life: The Science of Biology, 4th Edition
The wildly complex life cycle continued
7
8
Purves et al., Life: The Science of Biology, 4th Edition
Had enough yet??
9
Purves et al., Life: The Science of Biology, 4th Edition
Now we get to the troublesome stage
Cycles of replication inside red blood cells
Lead to cycles of fever and chills
And aggregated blood cells block blood vessels
10
Purves et al., Life: The Science of Biology, 4th Edition
We also need to get back to the next mosquito to complete the cycle
11
Purves et al., Life: The Science of Biology, 4th Edition
Here’s GlaxoSmithKline’s
Cliff Notes
version