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“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,

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slide1

“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

slide2

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)

slide3

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)

slide4

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)

slide6

Like HIV and TB, malaria is

  • unequally distributed, even in the tropics
slide7

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

slide9

It’s especially hard on kids

75% of the deaths are among African children

what is malaria
What Is malaria?
  • A mosquito-borne infectious disease caused by Protozoan parasites of the genus Plasmodium
what is malaria12
What Is malaria?
  • Transmitted only by Anopheles Mosquitoes

(>60 species!)

Seattle Biomedical Research Institute

what is malaria13
What Is malaria?
  • The Disease can be Acute or Chronic
acute symptoms
Acute Symptoms
  • Classical features include cyclic symptoms
    • Cold stage: chills and shaking
    • Hot stage: fever, headache, vomiting, seizures in children
    • Sweating stage: weakness
    • Feel well for period of time, then cycle repeats itself

www.uhhg.org/mcrh/resources/video/malariappt.pdf

each disease has a distinct course18
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 course19
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
Each disease also has a distinct geographical distribution

www.uhhg.org/mcrh/resources/video/malariappt.pdf

each disease also has a distinct geographical distribution21
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 distribution22
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
Malaria damages the bodyin 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 ways25
Malaria damages the bodyin 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 ways26
Malaria damages the bodyin 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 ways27
Malaria damages the bodyin a number of ways

In severe cases 20% of patients can die,

even with the best care

slide28

DIAGNOSIS

  • Gold standard: Multiple thick and thin smears
malaria is not currently a serious threat in the us
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

slide32

Although….

www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf

not that long ago
Not that long ago….

www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf

it could come back
It could come back!

www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf

slide39

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

slide40

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

slide41

So just who

is this

Plasmodium?

www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf

slide42

It’s not a

bacterium or

virus but a

eukaryote

like us

www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf

slide43

However,

unlike us

it lives a

solitary life

as a single

cell

www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf

slide45

Let’s go back to the family tree

http://drnelson.utmem.edu/Woods.Hole/slide5.png

slide46

Let’s go back to the family tree

You and me

http://drnelson.utmem.edu/Woods.Hole/slide5.png

slide47

mushrooms

You and me

http://drnelson.utmem.edu/Woods.Hole/slide5.png

slide48

mushrooms

You and me

plants

http://drnelson.utmem.edu/Woods.Hole/slide5.png

slide49

We are family….

mushrooms

You and me

Plasmodium

plants

http://drnelson.utmem.edu/Woods.Hole/slide5.png

slide50

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

slide51

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

slide52

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??!

slide53

Plasmodium and its relatives

also have a specialized

Structure at one end of the cell

Involved in invading other cells

slide55

Plasmodium’s closer relatives

Include parasites causing

Babesiosis, Toxoplasmosis,

And Cryptosporidiosis

slide56

Plasmodium has a wildly complex life cycle

6

2

5

3

4

1

Purves et al., Life: The Science of Biology, 4th Edition

slide57

And that’s just in the mosquito!

6

2

5

3

4

1

Purves et al., Life: The Science of Biology, 4th Edition

slide58

The wildly complex life cycle continued

7

8

Purves et al., Life: The Science of Biology, 4th Edition

slide59

Had enough yet??

9

Purves et al., Life: The Science of Biology, 4th Edition

slide60

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

slide61

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

slide62

Here’s Glaxo-

SmithKline’s

Cliff Notes

version

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