6. Cholera

Question 1

What did cholera lead to the introduction of?

Answer 1

Quarantine

Question 2

Who traced back to where disease started and hypothesised that cholera was found in water?

Answer 2

John Snow @ the Broad Street Pump

Question 3

What is the bacterium responsible for Cholera

Answer 3

Vibrio cholera

Question 4

Name a common pandemic causing-strain of Vibrio cholera

Answer 4

V. cholerae O1 El Tor

Question 5

Does cholera have a high or low fatality rate?

Answer 5

High

Question 6

What theory was cholera central to the establishment of?

Answer 6

The germ theory of infection

Question 7

Characteristics of Vibrio cholerae

Answer 7

• Gram Negative
• Motile
• Curved rod
• Single, long, flagellum in vibrio cell - highly motile and can swim through motile aqueous environments

Question 8

What type of toxin does V. cholerea produce?

Answer 8

Complex A-B toxin

Question 9

How is cholera spread?

Answer 9

• Faeco - oral transmission

- Associated with unclean water, foods contained by handler or person to person transmission

Question 10

What serotype is responsible for the most recent outbreak of cholera?

Answer 10

V. cholerae O139

Question 11

Why is V. Cholerae unusual?

Answer 11

It has 2 chromosomes

• one large (3 mega bases)
• one small (1 mega bases)

Question 12

Which of the V. cholerae serotypes are toxogenic?

Answer 12

Type O1 and Type O193

Question 13

How do V. cholerae serotypes differ?

Answer 13

They are distinguished based on slight modifications to the O antigen (part of LPS) that they produce - responsible for different Ab profiles

Question 14

Is toxigenic V. cholerae that has gone through a host more or less virulent than toxigenic V. cholerae from the environment?

Answer 14

More virulent when it has gone through a host

Question 15

Can you use the vaccine for El Tor for O139?

Answer 15

No because they are antigenically distinct

Question 16

Symptoms of cholera

Answer 16

Profuse watery diarrhoea (up to 20 L/day) - 'rice water stool'
Abdominal cramps
Fever
Nausea
Vomiting

Question 17

What can happen if cholera is left untreated?

Answer 17

Can lead to dehydration, collapse of the circulatory system & death

Question 18

What is effective for cholera?

Answer 18

Early rehydration

Question 19

Fatality rate was as high as 50% in 1960s, now it’s only around 2%. Why is this?

Answer 19

Due to ORT (rehydration treatment)

Question 20

What is the term used to describe serious cases of cholera in which death can result in hours?

Answer 20

Cholera gravis

Question 21

High or low infectious dose for cholera?

Answer 21

High infectious dose

Question 22

True or False: V. cholerae is becoming resistant to clinically important antibiotics

Answer 22

True

Question 23

Virulence in cholera depends on which 2 factors?

Answer 23

Colonisation and toxin production

Question 24

Necessary characteristics for V. cholerae colonisation?

Answer 24

1. Motility - non-motile mutants are less virulent than the parenteral strains, important in stomach and gut
2. Pili: Tep (toxin co-regulated pili) mutants are avirulent
3. Haemagglutinin - an adhesin
4. Detachment - mucinase produced by V. cholerae, mucinase-mutants are less virulent than the parent

Question 25

What is the role of the A1 subunit of the complex A-B cholera toxin?

Answer 25

A1 contains the toxic activity

Question 26

What is the role of the A2 subunit of the complex A-B cholera toxin?

Answer 26

A2 associates with B subunits (5)

Question 27

What is the A subunit of the complex A-B cholera toxin?

Answer 27

An ADP ribosylase

Question 28

Is the A1 subunit attached to the A2 subunit?

Answer 28

Yes via a disulphide bridge, so that the A1 part can be released when the toxin is taken up into the target cell

Question 29

What does the B part of the cholera toxin bind?

Answer 29

GM1 ganglioside (surface sugar on epithelial cell) → endocytosis → A1 delivered into cytoplasm of epithelial cell

Question 30

What happens when the A part of the cholera toxin is internalised?

Answer 30

ADP ribosylates Gs
ADPR-Gs mimics GTP-Gs and activates AC
AC produces cAMP → ion channels open
Channel is ‘frozen open’ because ADPR cannot fall off so water is continuously lost (due to elevated cAMP levels)

Question 31

Is ORT just water?

Answer 31

No - it includes glucose, salts & water because ions are lost as well as water

Question 32

What are other toxins produced by V. cholerae?

Answer 32

• Zot toxin (zona occludens toxin) - disrupts the tight junctions between mucosal cells
• Ace toxin (accessory cholera toxin) - causes diarrhoea in animals, no known role in humans

Question 33

What is the treatment for cholera?

Answer 33

Oral rehydration therapy (ORT)

Question 34

What are cholera vaccines usually taken with, and why?

Answer 34

Cholera vaccines are usually taken with bicarbonate to neutralise acid in stomach

Question 35

Are cholera vaccines effective over long periods of time?

Answer 35

No, only useful to control outbreaks & epidemics

Question 36

What gene is a major player in cholera toxicity?

Answer 36

CFTR gene (because it controls ion and water flow into gut lumen

Question 37

Explain the heterozygote advantage that CF carriers have in related to cholera

Answer 37

Hypothesis that CF carriers (heterozygous for mutated gene - no associated disease) have lower levels of CFTR and are selected from in regions exposed to cholera. Thought that heterozygotes are protected from the most serious outcomes of a diarrhoeal disease because they have low levels of these CFTR channels. Also suggested that heterozygotes have an advantage in typhoid fever & TB.

Question 38

What blood group is thought to have increased disease severity without decrease in infection?

Answer 38

O blood group