“The awkward fact with which US policy wrestles is that

“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

Leading causes of death in Sub-Saharan Africa, South Asia, and Southeast Asia for persons age 0-44 (World Health Organization)

As you knowin the developing world treatable

infectious diseases remain big killers


Now it’s time to look at number 3:Malaria


That’s right: 300 million new cases per year

making it the most prevalent serious infectious disease!

–2.1 billion people live in MALARIOUS areas2.1 billion people live in MALARIOUS areas

–Like HIV and TB, malaria is Like HIV and TB, malaria is

–unequally distributed, even in the tropicsunequally distributed, even in the tropics

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

–In areas of Africa with high transmission In areas of Africa with high transmission –there are 2700 deaths per day = 2 per minutethere are 2700 deaths per day = 2 per minute

It’s especially hard on kids

It’s especially hard on kids

75% of the deaths are among African children75% 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 A mosquito-borne infectious disease caused by

Protozoan parasites of the genus Protozoan parasites of the genus PlasmodiumPlasmodium

What Is malaria? Transmitted only by Anopheles Mosquitoes Transmitted only by Anopheles Mosquitoes (>60 species!)(>60 species!)

Seattle Biomedical Research Institute

What Is malaria?

The Disease can be Acute or ChronicThe Disease can be Acute or Chronic

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


In fact it is several different diseases


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.



P.ovale and P.vivax

can cause chronic malaria,

reappearing after months or years

due to latent parasites in liver


Each disease also has a distinct geographical distribution






Malaria damages the bodyin a number of ways

Red blood cell destruction -> anemiaRed blood cell destruction -> anemia

Waves of parasites bursting red blood cellsWaves of parasites bursting red blood cells

Lead to classic cycles of fever and chillsLead to classic cycles of fever and chills


Changes adhesive properties of infectedChanges adhesive properties of infected

Red blood cells -> blocking blood vessels Red blood cells -> blocking blood vessels leading to Tissue hypoxialeading to Tissue hypoxia


If this happens in brain it is cerebral malariaIf this happens in brain it is cerebral malaria

which is often fatalwhich is often fatal

Blocking bloodBlocking blood

vessels can alsovessels can also

cause kidney failurecause kidney failure


In severe cases 20% of patients can die,In severe cases 20% of patients can die,

even with the best careeven with the best care

Gold standard: Multiple thick and thin smears

DIAGNOSIS


1300 cases in US per year1300 cases in US per year Essentially all “imported”Essentially all “imported” Also transfusion related malariaAlso transfusion related malaria

Malaria is not currently a serious threat in the US


Although….

Malaria is not currently a serious threat in the US

However, this was not always the case

Not that long ago….


It could come back!


Let step back and lookat the parasites that cause malaria

A French army doctor in A French army doctor in AlgeriaAlgeria observed observed parasites inside parasites inside red blood cellsred blood cells of malaria of malaria patients and proposed patients and proposed for the first time that a for the first time that a protozoan caused protozoan caused diseasedisease


It was discovered more than 100 years ago

Charles Louis Alphonse Laveran

http://en.wikipedia.org/wiki/Algeria

http://en.wikipedia.org/wiki/Red_blood_cell

http://en.wikipedia.org/wiki/Charles_Louis_Alphonse_Laveran


French army doctor in French army doctor in AlgeriaAlgeria observed observed parasites inside parasites inside red blood cellsred blood cells of malaria of malaria patients and proposed patients and proposed for the first time that a for the first time that a protozoan caused protozoan caused diseasedisease


Charles Louis Alphonse Laveran

1907 1907 Nobel Prize for Physiology

or Medicine!!

http://en.wikipedia.org/wiki/Algeria

http://en.wikipedia.org/wiki/Red_blood_cell



http://en.wikipedia.org/wiki/Nobel_Prize_for_Physiology_or_Medicine





So just who

is this

Plasmodium?


It’s not a

bacterium or

virus but a

eukaryote

like us


However,

unlike us

it lives a

solitary life

as a single

cell

Let’s go back to the family tree

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




You and me


You and memushrooms


You and memushrooms

plants


We are family….You and me

mushrooms

plants

Plasmodium


They are on the same region of

the eukaryote tree as plants

You and me

plants

Plasmodium

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 cellsWe 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


Plasmodium’s closer relatives

Include parasites causing

Babesiosis, Toxoplasmosis,

And Cryptosporidiosis

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

Plasmodium has a wildly complex life cycle

2

3

4

5

1

6


And that’s just in the mosquito!

2

3

4

5

1

6


7

8

The wildly complex life cycle continued


9

Had enough yet??


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


We also need to get back to the next mosquito to complete the cycle

11

Here’s Glaxo-

SmithKline’s

Cliff Notes

version

Documents

“The awkward fact with which US policy wrestles is that