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MB3001 > L7 Cholera > Flashcards

L7 Cholera Flashcards

1
Q

Cholera lead the idea of…

A

Quarantine

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2
Q

High or low fatality rate with cholera?

A

High

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3
Q

What is a common pandemic-causing strain of Vibrio cholerae?

A

V. cholerae O1 El Tor

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4
Q

Who hypothesised that cholera was in the water?

A

John Snow

Broad St. pump

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5
Q

What theory was cholera central to the establishment of?

A

The Germ Theory of Infection

promoted establishment of public health systems

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6
Q

Features of Vibrio cholerae

A
  • Gram negative
  • Motile
  • Curved rod
  • Single, long, polar flagellum in vibrio cell - highly motile, can swim through aqueous environments
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7
Q

What type of toxin does V. cholerae produce?

A

Complex A-B toxin

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8
Q

How is cholera spread?

A

Faeco-oral transmission

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9
Q

How is V. cholerae unusual?

A

It has 2 chromosomes

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10
Q

Which are the only subsets of V. cholerae that are toxigenic?

A

O1 and O139

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11
Q

How do V. cholerae serotypes differ?

A

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

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12
Q

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

A

More virulent when it has gone through a host

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13
Q

Can you use the vaccine for El Tor for O139?

A

No because they are antigenically distinct

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14
Q

Symptoms of cholera

A 
Profuse watery diarrhoea (up to 20 L/day) - 'rice water stool'
Abdominal cramps
Fever
Nausea
Vomiting
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15
Q

What can happen if cholera is left untreated?

A

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

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16
Q

What is effective for cholera?

A

Early rehydration

17
Q

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

A

Due to ORT

18
Q

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

A

Cholera gravis

19
Q

High or low infectious dose for cholera?

A

High infectious dose

20
Q

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

A

True

21
Q

Virulence in cholera depends on which 2 factors?

A

Colonisation and toxin production

22
Q

Necessary characteristics for V. cholerae colonisation?

A
  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
23
Q

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

A

A1 contains the toxic activity

24
Q

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

A

A2 associates with B subunits (5)

25
Q

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

A

An ADP ribosylase

26
Q

Is the A1 subunit attached to the A2 subunit?

A

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

27
Q

What does the B part of the cholera toxin bind?

A

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

28
Q

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

A

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)

29
Q

Is ORT just water?

A

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

30
Q

What are other toxins produced by V. cholerae?

A
  • 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
31
Q

What is the treatment for cholera?

A

Oral rehydration therapy (ORT)

32
Q

What are cholera vaccines usually taken with, and why?

A

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

33
Q

Are cholera vaccines effective over long periods of time?

A

No, only useful to control outbreaks & epidemics

34
Q

What gene is a major player in cholera toxicity?

A

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

35
Q

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

A

Hypothesis that CF carriers (heterozygous for mutated gene - no associated disease) have lower levels of CFTR and are selected for 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.

36
Q

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

A

O blood group

MB3001 (15 decks)

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