Eukaryotic parasites 3: malaria

Question 1

Can malaria be trasnmitted through person-to-person contact?

Answer 1

No

Transmitted by mosquitoes

Question 2

What are the two major types of malaria?

Answer 2

P.falciparum

P.vivax

Question 3

Which populations are at the greatest risk of malaria?

Answer 3

Young children

Pregnant women

Question 4

Briefly describe the global burden of malaria?

Answer 4

Up to 1 million deaths per year

300-500 million cases per year

A leading cause of childhood deaths

Compounds poverty

Impedes economic development and education

Question 5

Describe the consequences of malaria during pregnancy?

Answer 5

Low birth weight

Miscarriages and stillbirths

Question 6

Which communities are most affected by malaria?

Answer 6

Resource-poor communities

Question 7

Describe the major obstacles to combatting malaria?

Answer 7

No highly effective control measures available

No vaccine

Drug resistance

Insecticide resistance

Question 8

Which Plasmodium species causes the majority of severe malaria and death?

Answer 8

P.falciparum

Question 9

Which Plasmodium species has a dormant liver stage?

Answer 9

P.vivax

Question 10

Which type of mosquito transmits malaria?

Answer 10

Female Anopheles mosquitoes

Question 11

During which stages of the malaria life cycle is disease present?

Answer 11

Only during the blood stage

Question 12

Describe the life cycle of P.falciparum?

Answer 12

Mosquito injects sporozoites > travel to liver> incubate 7-10 days in hepatocyte, replicate > merozoites burst out of liver > infect RBCs

Question 13

What are the immune responses to malaria mainly directed against?

Answer 13

Blood stage parasites

Question 14

What are the two clinical types of malaria?

Answer 14

Uncomplicated/mild malaria

Severe malaria

Question 15

Describe the clinical features of uncomplicated/mild malaria?

Answer 15

Flu-like illness

Fever, headaches, malaise

Question 16

Describe the clinical features of severe malaria?

Answer 16

3 MAIN FEATURES

Severe anaemia

Cerebral complications (coma, convulsions)

Respiratory distress and metabolic acidosis

OTHER

Hypoglycaemia, kidney failure, blood clotting problems

Question 17

Describe the treatment of uncomplicated/mild malaria?

Answer 17

Short course of anti-malarial tablets (3 days)

Clearance of P.vivax liver stage (14 days)

Question 18

What is the problem with using anti-malarial tablets?

Answer 18

Resistance emerging

Access

Counterfeit drugs

Question 19

Describe the treatment for severe malaria?

Answer 19

Anti-malarials: IV artemisinin or quinine (7-10 days)

Supportive treatment: fluids, blood transfusion, etc.

Question 20

Describe how severe malaria develops?

Answer 20

Unrestricted replication> parasites accumulate in vital organs, inflammatory response, RBC destruction > severe illness

Question 21

Describe the three main types of immunity to malaria?

Answer 21

1) Immunity that prevents severe malaria
2) Immunity that prevents any malria
3) Immunity to malaria in pregnancy

Question 22

Is the development of immunity to malaria slow or rapid?

Why?

Answer 22

Slow

PARASITE FACTORS

Multiple antigenic targets

Antigenic diversity

Antigenic variation

HOST FACTORS

Inadequate response

Non-functional/irrelevant responses

Poor development of memory

Question 23

Describe the factors which contribute to immunity and resistance to malaria?

Answer 23

Genetic: sickle-cell trait, alpha-thalassemia

Innate immunity: plasma factors (e.g. complement), innate cellular responses (e.g. NK cells), activated macrophages

Acquired immunity

Question 24

Describe the targets, and their mediators, of acquired immunity to malaria?

Answer 24

Sporozoites: Abs and T cells

Infected hepatocytes: T cells

Merozoites: Abs

Infected RBCs: Abs and T cells

Question 25

Describe the immune responses to sporozoites?

Answer 25

Abs inhibit infection of hepatocytes

Question 26

Describe the immune response to the liver stage of malaria?

Answer 26

CD8 T cells against infected hepatocytes

Question 27

Describe the immune responses to the blood stage of malaria?

Answer 27

CELL-MEDIATED RESPONSES CD4 T cells for protection Splenic clearnace of parasitsed RBCs (monocytes and macrophages) IFNY production for protection Pro-inflammatory cytokine production in severe disease ANTIBODIES TO MEROZOITES Inhibit RBC invasion and growth ANTIBODIES TO INFECTED RBCs Opsonisation for phagocytosis

Question 28

What part of the immune response to malaria is the key focus of most vaccines?

Answer 28

Abs to merozoites

Question 29

How can invasion of RBCs by malaria parasites be inhibited?

Answer 29

Antibodies Drugs

Question 30

Describe why a lack of effective immunity to malaria may arise?

Answer 30

Wrong immune response e.g. Abs to liver stage of P.falciparum Wrong target antigen e.g. antigens that are not essential for invasion or attachment Right antigens, wrong epitope e.g. sites that are not involved in invasion/attachment Antigenic diversity

Question 31

What are the three strategies to developing a vaccine against malaria?

Answer 31

1) Sporozoites/liver stages 2) Merozoites 3) Transmission blocking vaccines

Question 32

Describe the sporozoite/liver stage strategy to developing a vaccine for malaria?

Answer 32

Abs block entry to liver CD8 T cells inhiibt parasite development in liver Prevents parasites from entering bloodstream

Question 33

Describe the merozoite approach to developing a vaccine for malaria?

Answer 33

Abs opsonise merozoites for phagocytic clearance Blocks infection of RBCs, prevents replication in bloodstream

Question 34

Describe the transmission blocking approach to developing a vaccine for malaria?

Answer 34

Stop infection of mosquitoes Stops transmission, but does not help host

Question 35

Which is currently the most advanced vaccine for malaria?

Answer 35

RTS,S vaccine Phase 3 trial

Question 36

Describe the RTS,S vaccine?

Answer 36

Segment of CS protein (major Ag of sporozoites) Presneted in virus like particle with Hep B surface Ag Uses potent adjuvants

Question 37

Describe the difference in the acquired immune response to the blood stage and liver stage of malaria?

Answer 37

Blood stages mainly involve antibodies Liver stages mainly involve T cells