Malaria

Question 1

Which species of Plasmodium commonly cause mild disease?

Answer 1

P. ovale and P. malariae

Question 2

What transmits malaria?

Answer 2

Anopheles

Question 3

What are some of the symptoms of severe malaria?

Answer 3

Severe anaemia
Cerebral complications (coma, convulsions, longterm deficits)
Respiratory distress and metabolic acidosis (leading to reduced tissue perfusion and lung damage)
Hypoglycaemia
Kidney failure
Clotting disorders

Question 4

How is mild malaria treated?

Answer 4

Short course of effective anti-malarial tablets
ACT
Primaquine to clear P. vivax dormant liver stage

Question 5

What is ACT?

Answer 5

Artemisinin combination therapy (e.g. artemether-lumefantrine, AL)
Older drugs used to treat malaria include chloroquine, sulfadozine-pyrimethamine

Question 6

How is the dormant liver stage in P. vivax clear pharmacologically?

Answer 6

Using primaquine

Question 7

How is severe malaria treated?

Answer 7

7-10 IV anti-malarials (artemisinin, quinones)
IV fluids and supportive therapy in intensive care
Blood transfusion if required
Anti-convulsant, anti-coagulant, anti-inflammatory drugs as required

Question 8

What causes the development of malaria illness?

Answer 8

Accumulation of parasites in vital organs
Inflammatory responses
Destruction of RBCs (severe anaemia)

Question 9

What are the parasite factors responsible for slow development of immunity to malaria?

Answer 9

Multiple antigenic targets (~5000 genes)
Antigenic diversity (major targets show substantial polymorphism)
Antigenic variation (gene families allow switching to evade responses)

Question 10

What are the host factors responsible for slow development of immunity to malaria?

Answer 10

Inadequate response (especially in young children)
Non-functional/irrelevant responses
Poor development of memory responses?

Question 11

What does the antigenic variation and diversity of Plasmodium mean clinically?

Answer 11

Enables chronic and recrudescent infections, as well as repeat infections

Question 12

What are the most immune important responses for malaria?

Answer 12

Neutralising, opsonising and complement-activating antibodies
CD8+, CD4+ T cells
Activated macrophages

Question 13

Give 3 examples of genetic factors conferring resistance to malaria

Answer 13

Sickle cell
a-thalassaemia
Blood groups

Question 14

What are the targets and mediators in acquired immunity to sporozoites?

Answer 14

Abs inhibit infection of hepatocytes

T cells

Question 15

What are the targets and mediators in acquired immunity to infected hepatocytes?

Answer 15

CD8+ T cells against infected hepatocytes (limited response, perhaps due to low parasite load and short duration of infection)

Question 16

What are the targets and mediators in acquired immunity to merozoites?

Answer 16

Abs inhibit RBC invasion and growth directly and via ADCC (due to interaction with monocytes and macrophages)

Question 17

What are the targets and mediators in acquired immunity to infected RBCs?

Answer 17

Abs (opsonise RBCs expressing parasite Ag on surface)
CD4+ T cells (no MHC so no CD8+)
IFN-y production associated with severe disease
Pro-inflammatory cytokine response (e.g. TNF-a)
Monocytes and macrophages clear infected RBCs (mainly in spleen)

Question 18

What may the lack of effective immunity arise from?

Answer 18

Wrong immune response (e.g. Abs to liver stage)
Wrong target Ag (e.g. Ags not essential for invasion/attachment, or IC Ags)
Right Ag, wrong epitope (e.g. sites not involved in invasion/attachment)
Right target, right epitope but Ag diversity changes it quickly
Inability to mount a response to a specific Ag/epitope

Question 19

What is the Ag used in the experimental RTS, S vaccine? How is it presented?

Answer 19

Segment of CS protein

Presented in a virus-like particle with HBsAg to induce immune response

Question 20

What is the CS protein?

Answer 20

Major Ag of sporozoites

Question 21

How can the RTS, S vaccine possible be improved?

Answer 21

Adding a merozoite Ag (back-up if sporozoites get through to infect hepatocytes)