L7 Cholera Flashcards by Amy Ahern

Cholera lead the idea of…

Quarantine

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High or low fatality rate with cholera?

High

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

V. cholerae O1 El Tor

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Who hypothesised that cholera was in the water?

John Snow

Broad St. pump

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What theory was cholera central to the establishment of?

The Germ Theory of Infection

promoted establishment of public health systems

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Features of Vibrio cholerae

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

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What type of toxin does V. cholerae produce?

Complex A-B toxin

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How is cholera spread?

Faeco-oral transmission

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How is V. cholerae unusual?

It has 2 chromosomes

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

O1 and O139

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How do V. cholerae serotypes differ?

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

More virulent when it has gone through a host

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Can you use the vaccine for El Tor for O139?

No because they are antigenically distinct

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Symptoms of cholera

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

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What can happen if cholera is left untreated?

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

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What is effective for cholera?

Early rehydration

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

Due to ORT

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

Cholera gravis

High or low infectious dose for cholera?

High infectious dose

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

True

Virulence in cholera depends on which 2 factors?

Colonisation and toxin production

Necessary characteristics for V. cholerae colonisation?

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

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

A1 contains the toxic activity

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

A2 associates with B subunits (5)

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

An ADP ribosylase

Is the A1 subunit attached to the A2 subunit?

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

What does the B part of the cholera toxin bind?

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

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

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)

Is ORT just water?

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

What are other toxins produced by V. cholerae?

- 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

What is the treatment for cholera?

Oral rehydration therapy (ORT)

What are cholera vaccines usually taken with, and why?

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

Are cholera vaccines effective over long periods of time?

No, only useful to control outbreaks & epidemics

What gene is a major player in cholera toxicity?

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

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

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.

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

O blood group