Lecture 17 - More Malaria

Question 1

Greatest single factor contributing to infant death

Answer 1

Low birth weight

Question 2

Percentage of cases that are mild malaria

Answer 2

~95%

Question 3

Population at risk of P. falciparum

Answer 3

2.2 billion

Question 4

Population at risk of P. vivax

Answer 4

2.6 billion

Question 5

Type of plasmodium with a dormant liver stage

Answer 5

P. vivax

Question 6

Malarial species with mild symptoms, limited geographic distribution

Answer 6

P. malariae and P. ovale

Question 7

What is the main immune response to malarial infection?

Answer 7

Cellular and humoral response

Against blood stage

Question 8

Symptoms of mild malaria

Answer 8

Flu-like symptoms

Fever, chills, headache, malaise

Question 9

Severe malaria symptoms
1)
2)
3)
4)
5)
6)
7)

Answer 9

1) Severe anaemia
2) Cerebral complications
3) Respiratory distress
4) Metabolic acidosis
5) Hypoglycaemia
6) BLood clotting problems
7) Kidney damage

Question 10

Severe malaria cerebral complications

Answer 10

Coma, convulsions, potential long-term neurological problems

Question 11

Treatment for mild malaria

Answer 11

Three-day course of effective antimalarials
Aremisinin-combination therapy

Primaquine to clear P. vivax liver stage

Question 12

Treatment for severe malaria
1)
2)
3)

Answer 12

1) 7-10 days IV anti-malarials (quinine or artemisinin)
2) IV fluids, blood transfusion if required
3) Intensive care

Question 13

Peaks in malarial disease by age
1)
2)
3)

Answer 13

1) 0-5 years - Peak in severe malaria
2) 17-30 women - Pregnancy
3) Symptomatic malaria peaks between 0-5 years, declines rapidly as immunity mounts

Question 14

Why does immunity to malaria develop slowly?

1) a, b, c
2) a, b, c

Answer 14

1) Parasite factors
a) Over 5000 genes - many antigenic targets
b) Antigenic diversity - major polymorphism in major targets
c) Antigenic variation - var genes can recombine to avoid immune response
2) Host factors
a) Poor immune response in young children
b) DEvelopment of irrelevant immune responses
c) Poor development of memory response

Question 15

Development of malarial illness
1)
2)
3)
4)

Answer 15

1) Uncontrolled proliferation and release of merozoites in blood
2) Parasite accunulates in vital organs
3) Inflammatory responses
4) Destruction of red blood cells

Question 16

Recrudescent infection

Answer 16

An infection that recurs from a dormant stage

EG: P. vivax

Question 17

Do PfEMP1 genes vary between genomes?

Answer 17

Yes

Question 18

Number of var genes in existence

Answer 18

Thousands exist between all Plasmodium parasites

Question 19

Antigenic diversity of var genes compared to genetic sequences

Answer 19

Less diverse

Although around 60 var genes in a single parasite, there is a lot of redundancy, conserved sequences

Question 20

Effect of different var genes

Answer 20

Bind to different markers on endothelial wall, detected by different antibodies, T cells, etc

Different PfEMP1 expression allows infection of different organs

Question 21

Amount of blood volume going through spleen each minute

Answer 21

~5% of blood volume is processed by spleen each minute

Question 22

Different immune responses to infection
1)
2)

Answer 22

1) Antibodies against merozoites - Prevents invasion of erythrocytes, growth.
2) Antibodies against infected erythrocytes - opsonisation, phagocytosis

Question 23

Pregnancy and malaria
1)
2)
3)

Answer 23

1) Malaria infection occurs even if immunity is present
2) Greater density of parasitaemia
3) Risk of malaria decreases with each pregnancy

Question 24

Why can an otherwise immune woman be infected with malaria when pregnant?

Answer 24

1) PfEMP1 expressed to CSA, HA in placental endothelial walls allows adherence in placenta
2) No antibodies have been made against this, as it hasn’t been encountered by the woman’s immune system

Question 25

PfEMP1 variant that infects placenta

Answer 25

var2csa

Binds chondroitin sulphate A (CSA, a carbohydrate)

Question 26

Possible malaria vaccines
1)
2)

Answer 26

1) Possible to make a vaccine for pregnant women, as placental malaria only express var2csa
2) Difficult to make general malaria vaccine, as would have to include many different PfEMP1 variants