Malaria

Question 1

History of malaria:

Answer 1

• Literally means bad air
• Hippocrates described clinical symptoms
• Jesuit brother Salumbrino observed bark of cinchona tree against it

Question 2

What causes malaria?

Answer 2

Plasmodium parasites

Question 3

Where does stand malaria stand on the eukaryotic tree?

Answer 3

TSAR, Sar, Alveolata, Apicomplexa, Plasmodium

Question 4

What are the 4 different types of Plasmodium causing malaria?

Answer 4

• Plasmodium falciparum
• Plasmodium vivax
• Plasmodium malariae
• Plasmodium ovale

Question 5

What is the distribution of Plasmodium falciparum?

Answer 5

• 90% in africa

- 50% in South-East Asia

Question 6

What is the distribution of Plasmodium vivax?

Answer 6

90% in Asia, South America

50% in South-East Asia

Question 7

What is the distribution of Plasmodium malariae?

Answer 7

2% in Africa

Sporadic in Asia and South America

Question 8

What is the distribution of Plasmodium ovale?

Answer 8

8% in Africa

Question 9

What are the distinguishing features of Plasmodium falciparum?

Answer 9

Majority of deaths globally

Causes cerebral malaria

Question 10

Is Plasmodium falciparum dormant in liver stage?

Answer 10

No

Question 11

What are the distinguishing features of Plasmodium vivax?

Answer 11

Immunity of people with Duffy antigen

Severe malaria in 1/5 cases

Question 12

Is Plasmodium vivax dormant in liver stage?

Answer 12

Yes

Question 13

What are the distinguishing features of Plasmodium malariae?

Answer 13

Milder symptoms

Question 14

Is Plasmodium malariae dormant in liver stage?

Answer 14

No

Question 15

What are the distinguishing features of Plasmodium ovale?

Answer 15

Milder symptoms

Question 16

Is Plasmodium ovale dormant in liver stage?

Answer 16

Yes

Question 17

Summaries the global impact of malaria?

Answer 17

300-500 million cases
1.5-2.7 million deaths per year
Eradicated from temperate zones
80% of cases concentrated in 15 countries 
82% deaths are children in sub-Saharan

Question 18

What is malaria?

Answer 18

Vector borne disease

Question 19

Why is malaria a vector borne disease?

Answer 19

• Insect vector
• Human host
• Transmitted by anopheline mosquitoes
• Female only
• No animal reservoir

Question 20

Define sporozoites:

Answer 20

Motile spore-like stage in like cycle of parasitic sporozoans
Typically infective introduced into host

Question 21

Define merozoites:

Answer 21

Non-motile stage

Question 22

Define trophozoite:

Answer 22

Activated, feeding stage in the life cycle of certain protozoan parasites

Question 23

Define hypnozoite:

Answer 23

sleeping stage

Question 24

Describe the Plasmodium life cycle:

Answer 24

1. Sporozoite in salivary hangs - infected with salvia
2. Invade liver cells - within 30 to 60 minutes
3. In hepatocyte divide asexually leading to schizonts in 6 to 7 days
4. Each schizonts in hepatocyte = gives birth to to 1000s of merozoites released into blood from ruptured hepatocytes
5. Merozoites actively invade red blood cells
6. Trophozoite: parasite ingest the cytoplasm
7. Schizont stage: Schizogony - asexual replication involving nuclear division without cytoplasmic division followed by budding to form merozoite
8. Invade new erythrocytes
9. Red blood cells: parasites enter sexual cycle and differentiate into micro or macro gametocytes which circulate into the blood

Question 25

What does the apex of sporozoite and merozoite contain?

Answer 25

Complex organelles specialised for penetrating host cells and tissues Apicoplasts (type of plastids)

Question 26

What is crucial for malaria infection?

Answer 26

Liver cell invasion by sporozoites

Question 27

Why are liver cell invasion by sporozoites is crucial for infections?

Answer 27

- Plasmodium sporozoites migrate through several hepatocytes before infecting a final one - Migration through hepatocytes occur by breaching their plasma membranes - Sporozoites do not have flagella - migration uses the actin cytoskeleton

Question 28

What does merozoites actively invade?

Answer 28

Red blood cells

Question 29

How do merozoites actively invade red blood cells?

Answer 29

- Plasmodium app target erythrocytes of different ages - Specific engagement of erythrocyte receptors define target cell tropism - Downstream events result in physical penetration of erythrocyte (powered by parasite actomyosin cytoskeleton)

Question 30

How does Plasmodium infection lead to disease?

Answer 30

- Malaria is associated with regular episodes of fever | - Occurs during simultaneous bursting of infected red blood cells

Question 31

What is the advantage of life in a red blood cells?

Answer 31

- Red blood cell is rigid = supports shear stress exerted by blood flow - Parasite is hidden from the immune system

Question 32

What is the disadvantage of life in a red blood cells?

Answer 32

- Nutrient-poor environment - Cells have relative short life - Cells are continuously recycled in the liver/spleen = exposed to the immune system

Question 33

What are three modifications of red blood cells by Plasmodium falciparum?

Answer 33

1. Promote formation of new channels for the import and export of nutrients 2. Break down haemoglobin into amino acids 3. Place adhesive proteins on surface of infected red blood cells that induce rosetting and adherence to the endothelium avoiding clearance by host

Question 34

What are key survival factor for Plasmodium in its human host?

Answer 34

Protein PfEMP1

Question 35

What does PfEMP1 stand for?

Answer 35

Plasmodium falciparum erythrocytes membrane protein 1

Question 36

What does PfEMP1 do?

Answer 36

- Ligand to bind receptors on endothelial cells - Infected cells adhere to the endothelium - Sequestration can obstruct blood vessels - Leads to haemorrhage and hypoxia - Cerebral malaria (most severe form of the disease) - haemorrhage and rupture of blood brain barrier

Question 37

What does Plasmodium exhibits?

Answer 37

Antigenic variation

Question 38

What are PfEMP1 proteins?

Answer 38

Encoded by a large multigenerational family called var

Question 39

How many different genes each produce a different PfEMP1?

Answer 39

60

Question 40

What does recombination of genes allow of PfEMP1s?

Answer 40

Creation of new varients

Question 41

What does switching between different PfEMP1 variants present?

Answer 41

Host from mounting an effective immune response

Question 42

Why is the vaccine development against malaria difficult?

Answer 42

Switching between different variants

Question 43

What is the only vaccine approved?

Answer 43

RTS,S

Question 44

What does RTS,S require?

Answer 44

Four infections and relatively low efficacy

Question 45

When does WHO not recommend to use RTS,S vaccine?

Answer 45

In babies between 6 to 12 weeks of age

Question 46

How do you control vector control?

Answer 46

- No animal reservoir - Insecticide impregnated mosquito nets and clothing - Sleep under ITN - Indoor residual spraying

Question 47

How is malaria diagnosed?

Answer 47

- Examining stained blood smears | - Rapid diagnostic tests also available

Question 48

What is an issue with malaria diagnostics?

Answer 48

False negatives

Question 49

What are malaria treatments?

Answer 49

-Drugs viable (quinine, chloroquine, artemisinin)

Question 50

What are problems of malaria treatments?

Answer 50

Resistance of parasites