Malaria

Question 1

What type of organisms are malaria

Answer 1

Eukaryotic protozoan

Question 2

How is malaria plasmodium spread?

Answer 2

Via female Anopheles mosquito

Question 3

What genus is malarial protozoan under?

Answer 3

Plasmodium

Question 4

What is Sporozoite

Answer 4

First stage of infection transmitted from the mosquiro to the human host

Question 5

What are 5 specied of plasmodium that can infect humans

Answer 5

P. vivax
P. ovale 
P. malariae 
P. falciparum 
P. knowlesi

Question 6

Why should we care about malaria?

Answer 6

2.4 billion people are exposed. 200-300 million new cases a year. Most predominant in Sub-Saharan Africa

Question 7

Where is P. vivax most present?

Answer 7

In Southeast Asia and Pacific Islands.

Africans don’t have receptor on RBC for P. vivax

130-400 million cases anually.

Question 8

Where is P. falciparum most pesent?

Answer 8

In Sub-Saharan Africa

90% of people are exposed
80% of clinical cases of P. falciparum are from here.

120 million cases anually

Question 9

UK cases of malaria

Answer 9

1500 new cases recently, has been on the uprise

Mostly P. falciparum but P. vivax is on the rise

Question 10

Clinical presentation of malaria

Answer 10

Similar to viral infections.

Symptoms occur in cyclic manner and matches stage in replication cycle.

Fever peaks 36-72 hours depending on strain of plasmodium.

Schizont ruptures to release toxins that cause fever

Question 11

Diagnosis

Answer 11

Gold standard is looking at blood sample under a microscope.
Sample is stretched air dried, fixed with ethanol and stained.

Also can do dipstick test of urine (inaccurate) or PCR (expensive and time consuming)

ELISA observing the reaction between parasite specific antigen and antibody.

Question 12

Treatment

Answer 12

Quinine and Riamet for P. falciparum and unkown

Chloroquine for P. malariae and P. knowlesi

P. vivax has developed resistant strains in Malaysia so need Primaquine

Combination therapy also used in response to increased resistance

Question 13

How does death occur in malaria

Answer 13

When trophozite or schizont occlude blood vessel in important part of the body

Question 14

What are hypnozoites

Answer 14

Dormant forms of plasmodium found in all malarial infections except P. falciparum

Question 15

What is the life cycle of P. falciparum plasmodium

Answer 15

Oocyte taken up into the saliva which matures sporozoite.

Sporozoite inoculated into host and travels to the liver, where it matures into trophozoite.

In the liver trophozoite undergoes asexual reproduction to form hepatic schizont.

Schizont ruptures by schizogeny to produce merozoite

In blood, merozoite attaches to RBC undergoes replicative cycle
Merozoite -> trophozoite -> schizont -> schizogony -> merozoites

Merozoite continues infecting RBC until triggers the immune system

Parasites differentiate into gametocytes

Question 16

What happens when a mosquito bites an infected person?

Answer 16

Takes up the female and male gametocytes to form the oocyte

Question 17

Is the liver phase symptomatic?

Answer 17

No

Question 18

When does infection occur in malaria

Answer 18

Once the has bound to the RBC

Question 19

How does schizont rupture lead to pathogenesis of malaria?

Answer 19

Triggers sentinel cells that cause inflammation by the release of inflammatory mediators.

IFN g
TNF a
IL-1
IL-12

In low concentrations they are helpful, but when dysregulated cause heamolysis of RBC, failure to produce normal RBCs and anaemia.

Question 20

What is PfEMP1

Answer 20

P. falciparum Erythrocyte Membrane protein

Polymorphic proteins encoded by gene family VAR

Question 21

How does PfEMP cause disease?

Answer 21

Antibodies direct towards specific PfEMP, and sub-population alter their expression leading to reactivation and reinfection.

Also PfEMP bind to epithelial cells in blood vessels, occluding them.

Question 22

Consequences of occluded blood vessels

Answer 22

Fetal loss
Respiratory distress
Stroke
Heart attack

Question 23

Why is it difficult to eradicate plasmodium causing malaria

Answer 23

Sporozoite evades immune system

Latent forms are not targeted by drugs

Many years of repeated infection needed to gain sligh immunology

Question 24

Mechanisms of immune responses to malaria

Answer 24

Antibodies to sporozoite
IFN g and CD8 T cells inhibit parasite development in hepatic cells
Antibodies to merozoite
Antibodies to toxins
Kill parasites intracellularly during asexual RBC stage
Gametocytes coated in antigen
Antibodies that block PfEMP

Question 25

How is inhibition of sporozoites via CD8 T cells not effective

Answer 25

The CD8 T cells take some time to develop. Antibodies cannot enter the hepatocytes. During this time the sporozoite matures into merozoite and escapes to the bloodstream.

Question 26

How does IFN g destroy intracellular hepatic storozoite

Answer 26

NO dependent intracellular mechanism

Question 27

Why target the merozoite asexual reproduction stage?

Answer 27

Highest chance of eliminating the parasite. Agglutination by coating with ADC1 makes the cells more active and prone to phagocytosis.

Question 28

Why develop antibodies to toxins?

Answer 28

Reduce the inflammatory response

Question 29

Why develop antibodies to he gametocytes?

Answer 29

Prevent them from forming a zygote