Lecture 17 - More Malaria Flashcards Preview

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Flashcards in Lecture 17 - More Malaria Deck (26):
1

Greatest single factor contributing to infant death

Low birth weight

2

Percentage of cases that are mild malaria

~95%

3

Population at risk of P. falciparum

2.2 billion

4

Population at risk of P. vivax

2.6 billion

5

Type of plasmodium with a dormant liver stage

P. vivax

6

Malarial species with mild symptoms, limited geographic distribution

P. malariae and P. ovale

7

What is the main immune response to malarial infection?

Cellular and humoral response

Against blood stage

8

Symptoms of mild malaria

Flu-like symptoms
Fever, chills, headache, malaise

9

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

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

10

Severe malaria cerebral complications

Coma, convulsions, potential long-term neurological problems

11

Treatment for mild malaria

Three-day course of effective antimalarials
Aremisinin-combination therapy

Primaquine to clear P. vivax liver stage

12

Treatment for severe malaria
1)
2)
3)

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

13

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

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

14

Why does immunity to malaria develop slowly?
1) a, b, c
2) a, b, c

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

15

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

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

16

Recrudescent infection

An infection that recurs from a dormant stage
EG: P. vivax

17

Do PfEMP1 genes vary between genomes?

Yes

18

Number of var genes in existence

Thousands exist between all Plasmodium parasites

19

Antigenic diversity of var genes compared to genetic sequences

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

20

Effect of different var genes

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

Different PfEMP1 expression allows infection of different organs

21

Amount of blood volume going through spleen each minute

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

22

Different immune responses to infection
1)
2)

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

23

Pregnancy and malaria
1)
2)
3)

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

24

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

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

25

PfEMP1 variant that infects placenta

var2csa
Binds chondroitin sulphate A (CSA, a carbohydrate)

26

Possible malaria vaccines
1)
2)

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