Lecture 2- Malaria Flashcards
How many species of plasmodium are there?
> 100
And 4 transmitted to humans
What is the most widespread species of malaria parasites?
P. falciparum
What does malaria transmission require?
An average temperature of above 15 degrees C.
It cannot survive above 3000m
What are the 4 species transmitted to humans?
P. falciparum P. vivax P. ovale P. malariae (P. knowlesi has been recently found in humans)
What are the 4 phases of the life cycle?
One sexual without multiplication
Three asexual with multiplication
Why do you get splenomegaly with malaria?
Malaria is a blood-borne infection therefore the spleen grows to try mount the immune system
Which organisms transmit malaria?
FEMALE mosquitoes (males don't suck blood. The males have feathery antennae, females don't)
Main features of malaria life cycle?
- Female mosquito squirts anticoagulants into human along with sporozoites (infective stage).
- Sporozoites circulate and get into liver. Go through kuppler cells which line blood vessels of liver
- Change form into merozoite=rounded not worm like anymore
- Replicate (by about 20k)
- After 1 weekish, merozoites invade RBCs, now erythrocytic stage
- Replicate and then synchronous bursting out of RBCs, gives you fever ever 2/3 days
- Change into sexual stages. Have male and female gametocytes
- New mosquito sucks up those RBCs. Must have gametocytes to transmit infection
- Gametocytes unite into zygote
- Zygote becomes sporozoite and start again!
What are the two parts of the cycle?
- Exoerthrocytic stage- when in liver
2. Erythrocytic stage- in RBCs
What are the stages of the parasite?
Sporozoite in salivary glands of mosquito.
Turns into merozoite in liver.
Turn to Gametocytes in RBC
Then eaten by mosquito and Gametocytes unite into zygote and they turn into sporozoite which go to salivary gland again
Where do the four stages happen?
- The sexual phase and first asexual phase occur in Anopheline Mosquitoes
- The second asexual phase is in the liver
- The third asexual phase is in the blood (repeated many times)
How does every asexual phase begin?
With feeding and growth
How does every phase end?
When the new invasive parasites appear
In the third phase what happens to some parasites?
Some parasites become sex cells- the gametocytes- which start a new cycle if they get taken into Anopheles mosquitoes
What happens in the sexual phase? (in the mosquito that’s just fed on a person’s blood)
Ingested gametocytes: swell, discharge osmophilic bodies into RBC, this disrupts RBC membrane releases gametocytes
What happens during the development of the male gametocyte?
The DNA is replicated 3 times- so the nucleus of the activated gamete has 8 complete sets of DNA
Then 8 kinetosomes are formed in a microtubular organising centre. Each kinetosome is the base and growing point for flagellum (axoneme). 8 flagella are formed- gamete explodes releaseing flagellum
Exflagellation within minutes
What do the male gametocytes do?
Male gametocytes actively swim to females using their flagella.
Fertilise them-> turn into zygote.
Next few hours develop into OOKINETE (develops apical complex)
Ookinete can move, glides through blood meal and insect stomach wall, penetrates gut wall
What happens in first asexual phase?
ookinete to sporozoite
For malaria to invade, at every stage, what does it need?
An apical complex
What happens when ookinete turns to oocyte?
Oocyts project into haemocoel of insect- feeds on haemoglobin of blood meal.
DNA replication occurs
Each oocyst contains at least 1000 elongate SPOROZOITES
Burst out of sporocyst and migrate to salivary gland of mosquito
What happens after you become infected with sporozoites?
leave blood enter Kupffer cells which line liver capillaries. Then they leave these cells and go into hepatocytes.
So rapid growth - loses sporozoite morphology, rounds up and becomes TROPHOZOITE. 40µm in 48 hours.
Divides into 10,000 - 30,000
Schizogony/schizonts MEROZOITES.
INFECTED PERSON SHOWS NO SYMPTOMS
In P.vivax - some trophozoites become a latent stage called HYPNOZOITES - CAUSE RELAPSES - YEARS LATER
Third asexual phase in RBCs
Merozoites burst out of hepatocytes and invade RBCs
Once inside they ingest haemoglobin,
Become trophozoite, erythrocytic schizont, divides into merozoites. Symptoms synchronous when they bust out.
What are the steps of invasion of RBCs by merozoites?
- Receptor recognition and binding
2. Erythrocyte deformation
What does invasion of RBCs by merozoited depend on?
RBC glycophorins
Different malaria parasites depend on different proteins e.g. duffy group antigens for some
How does the parasite invade steps?
- Receptor Recognition:
- Initial attachment - anywhere
- Entry - following alignment of apical end
- Attachment by fibrils of parasite surface coat.
- Tight junction is formed subsequent invagination.
- PARASITOPHOROUS VACUOLE
NB: THICK SURFACE COAT NOT ENGULFED - SLOUGHED OFF
Does it go into the cytoplasm of the cell?
No!
Goes into parasitophorous vacuole
Which organelles are important for their apical complex and that contain enzymes to penetrate the RBC?
Rhopteries
Micronemes
Give example of molecule that helps invasion on RBC?
RESA molecule
(Ring erythrocyte surface antigen). It enhances the fluidity of the RBC membrane
What happens after entry of RBC?
Development of feeding stages
Trophozoites
Enzymes produced to degrade haemoglobin
Most dramatic changes= irregular shape and membrane knobs on RBC so more sticky at endothelium, slows parasites down allows to attach
What’s it called when the RBCs are too sticky and cause clots in brain?
Cerebral malaria
