02-02-23 - Bacterial and Viral Infections of the Gastrointestinal Tract

Question 1

Learning outcomes

Answer 1

• Recognise the clinical manifestations of infection in different parts of the gastrointestinal tract
• Recognise the different pathogens which cause infection through the gastrointestinal tract
• Identify the bacteria that cause diarrhoeal disease
• Identify the viruses that cause diarrhoeal disease
• Identify the bacteria that produce toxins in the GI tract and explain how they affect the host
• Describe ways in which to prevent bacterial and viral GI infections.

Question 2

Epidemiology of Bacterial and Viral Infections of the Gastrointestinal Tract.

How many deaths in children are due to diarrhoeal disease?

How does it affect developed countries and working days?

Answer 2

• Epidemiology of Bacterial and Viral Infections of the Gastrointestinal Tract
• Diarrhoeal disease is one of the leading causes of death among children under the age of 5
• More than 1 in 10 childhood deaths are due to diarrhoeal disease
• Major cause of economic loss in developed world
• 11 million working days lost per year in the UK

Question 3

What are 5 different examples of barriers to infection?

Answer 3

• 5 different examples of barriers to infection:

1) Eye – blinking, tears

2) Skin – Structural barrier, sweat sebum, normal flora

3) Urogenital tract – Acidity of urine and lavaging action of urine

4) Respiratory tract – Coughing and mucus

5) GI tract – stomach acidity, normal flora

Question 4

What is intoxication?

What is infection?

Answer 4

• Intoxication:
• Ingestion of food containing biologically active toxins which cause disease
• Infection:
• Ingestion of live microbes:
• Can multiply readily on food prior to consumption
• Use food only as a vector

Question 5

What are 5 different modes of transmission?

Answer 5

• 5 different modes of transmission:
  1) Faecal-oral (all of these boil down to this)
  2) Food
  3) Fluids
  4) Fingers
  5) Person-to-person

Question 6

What are 5 useful clues for determining aetiology (cause) besides history and examination?

Why is microbiological investigation difficult to use?

What are 2 culture methods can be used to improve diagnosis?

Answer 6

• 5 useful clues for determining aetiology (cause) besides history and examination:
  1) Dysentery (blood/mucus in stool),
  2) Vomiting
  3) Abdominal pain
  4) Travel or food history
  5) Speed of onset
• Microbiological investigation (stool culture) is like trying to find a needle in a haystack
• To improve diagnosis, different culture methods can be used:

1) Enrichment media
* Promote preferential growth of a pathogen

2) Differential media
* Differentiate micro-organisms by growing in presence of specific nutrients combined with an indicator that changes colour

Question 7

How are most infections resolved?

What are antibiotics reserved for?

What are 4 ways antibiotics can worsen disease?

Answer 7

• Most infections resolve spontaneously and only require fluid replacement
• Antibiotics are reserved for severe or prolonged symptoms
• 4 ways antibiotics can worsen disease:

1) Prolonging duration

2) Promoting toxin release
* Toxin released from bacteria faster when under stress e.g from antibiotics

3) Increasing antibiotic resistance

4) Disturbing natural flora

Question 8

How often can acute diarrhoea be treated with rehydration therapy?

What can be used for this?

What can function as an alternative?

What is an example of an oral rehydration solution?

Why are these substances used in oral rehydration therapy?

Answer 8

• 95% of cases of acute diarrhoea can be successfully treated with oral rehydration solution alone
• Electrolytes and glucose increase the resorption of fluids into the intestinal wall
• Fruit juices, coconut water, and other indigenous solutions are alternatives
• Example of an oral rehydration solution:
  1) 6 level teaspoons of sugar
  2) Half level teaspoon of salt
  3) 1 litre of water
• These substances are used in oral rehydration therapy as osmosis through the intestines is facilitated by the various inclusion of ions, such as sodium and glucose, which we can get from glucose and salt

Question 9

What are 4 personal measures for control of pathogen spread?

What are 4 public measures for control of pathogen spread?

Answer 9

• 4 personal measures for control of pathogen spread:
  1) Hand hygiene
  2) Cook foods properly
  3) Avoid cross contamination
  4) “Wash it, peel it, cook it or forget it”
• 4 public measures for control of pathogen spread:
  1) Pasteurisation of milk & dairy products
  2) Proper sewage disposal
  3) Provision of safe, clean drinking water
  4) Vaccination

Question 10

What are 3 examples of viral infections?

Answer 10

• 3 examples of viral infections:
  1) Norovirus
  2) Rotavirus
  3) Adenovirus

Question 11

Norovirus:
* Classification (1)
* Pathogenesis (3)
* Clinical presentation (6)
* How is norovirus transmitted?

Where do outbreaks occur?

What does continuing antigenic variation result in?

Answer 11

• Norovirus:
• Classification
  1) Single stranded RNA virus
• Pathogenesis
  1) Affects all ages and previously healthy
  2) Infectious dose very small (10-100 virions)
  3) Survives well in environment (including alcohol gel)
• Clinical presentation
  1) Projectile vomiting
  2) Diarrhoea
  3) Abdominal cramps
  4) Headache
  5) Muscle ache
  6) Infectious period from onset till 48 hours after symptoms stop
• Transmission by person to person (faecal-oral and aerosolised), foodborne, and water
• Outbreaks occur in hospitals, care homes, and cruise ships.
• Continuing antigenic variation results in immunity lasting less than a year (

Question 12

Rotavirus
* Classification (1)
* Pathogenesis (2)
* Clinical presentation (5)

What is rotavirus the most common cause of?

What groups does infection occur in?

When are rotavirus cases increased?

How is rotavirus transmitted?

What kind of vaccine is used for rotavirus?

Answer 12

• Rotavirus
• Classification (1)
  1) Double stranded RNA virus
• Pathogenesis (2)
  1) Mainly affect young children, elderly, and immunocompromised
  2) Infectious dose very small (10-100 virions)

Clinical presentation (5)
1) Watery diarrhoea
2) Vomiting
3) Abdominal cramps
4) Fever Incubation: 2 days
5) Duration of symptoms: 3-8 days

• Rotavirus is the most common cause of diarrhoeal illness in developing countries
• Infection occurs in children
• Increased cases in winter
• Transmission by person to person (faeco-oral or aerosolised)
• Effective live attenuated oral vaccine as part of the UK vaccination schedule

Question 13

Adenovirus
* Classification (1)
* Pathogenesis (2)
* Clinical presentation (1)

What does adenovirus account for 10% for?

Does it have seasonal incidence?

What groups is adenovirus symptomatic in?

How common are asymptomatic adenovirus infections?

Answer 13

• Adenovirus
• Classification (1)
  1) Double stranded DNA virus
• Pathogenesis (2)
  1) Mainly affect young children, elderly, and immunocompromised
  2) Infectious dose very small (10-100 virions)
• Clinical presentation (1)
  1) Mild prolonged diarrhoea
• Adenovirus is responsible for 10% of community-acquired diarrhoeas in young children
• Adenovirus has no seasonal incidence
• Only first infection symptomatic except in elderly and immunocompromised
• Asymptomatic infections common
• Although nearly everyone has been infected by age 5, only a few have had symptomatic infection

Question 14

What are 8 examples of gram-negative bacteria?

Answer 14

• 8 Examples of gram-negative bacteria:
  1) Campylobacter
  2) Vibrio cholerae
  3) Salmonella
  4) Shigella
  5) Escherichia coli
  6) Enterotoxigenic E. coli (ETEC)
  7) Enterohaemorrhagic E. coli (EHEC)
  8) Yersinia enterocolitica

Question 15

Campylobacter jejuni
* Classification (1)
* Pathogenesis (1)
* Clinical presentation (3)

How is Campylobacter jejuni transmitted?

Answer 15

• Campylobacter jejuni
• Classification (1)
  1) Gram negative curved bacilli with flagella
• Pathogenesis (1)
  1) Invasion of the bowel leads to inflammation and ulceration
• Clinical presentation (3)
  1) Bloody diarrhoea, abdominal pain and fever
  2) Incubation: 2-11 days
  3) Duration of symptoms: 3-21 days
• Campylobacter jejuni is the most common bacterial foodborne infection
• Transmitted via animals (poultry) and contaminated food

Question 16

Describe the Campylobacter Histological Appearance

Answer 16

• Campylobacter Histological Appearance
• Neutrophil rich inflammatory response involving the entire mucosa
• Villous atrophy and necrotic debris in crypts

Question 17

Vibrio cholerae
* Classification (3)
* Pathogenesis (2)
* Clinical presentation (5)

How large is the infective dose of Vibrio cholerae?

How does it spread?

How is it treated?

How does this affect mortality rates?

What are key preventative measures for Vibrio cholerae?

Answer 17

• Vibrio cholerae
• Classification (3)
  1) Gram negative bacilli
  2) Serotype O1 is the most common serotype
  3) Sucrose fermenter
• Pathogenesis (2)
  1) Polar flagella and mucinase facilitate penetration of intestinal mucous
  2) Disease caused by exotoxin – Protein ions pumped out of cell, causing massive fluid loss (in picture)
• Clinical presentation (5)
  1) Severe
  2) Profuse
  3) watery diarrhoea (rice water stool)
  4) Profound fluid and electrolyte loss
  5) Hypovolaemic shock and cardiac failure
• Vibrio cholerae is a human only pathogen with large infective dose *
• Spreads via contaminated food or water
• Prompt oral or intravenous rehydration is lifesaving - mortality <1% with treatment vs 40% without treatment
• Clean drinking water supply and proper sanitation are key preventative measures for vibrio cholerae

Question 18

Salmonella
* Classification (3)
* Pathogenesis (1)
* Clinical presentation (3)

Where is salmonella found?

How many serotypes does salmonella have?

What can certain serotypes cause?

How is salmonella transmitted?

Answer 18

• Salmonella
• Classification (3)
  1) Gram negative bacilli
  2) Member of the Enterobacteriaceae
  3) Non-lactose fermenter
• Pathogenesis (1)
  1) Invasion and inflammation of the bowel

Clinical presentation (3)
1) Watery diarrhoea, vomiting and fever
2) Incubation: 1-2 days
3) Duration of symptoms: 2-7 days

• Salmonella is found in a range of animals
• Salmonella has more than 2000 serotypes:
• S. typhi and paratyphi have only human reservoirs and can cause typhoid fever
• Transmission via contaminated food (especially meat and dairy), waterborne and person-to-person

Question 19

What are the 6 stages in the pathogenesis of Salmonella Infection?

Answer 19

• 6 stages in the pathogenesis of Salmonella Infection:

1) Ingestion of a large number of bacteria

2) Absorption into terminal ileum

3) Bacteria multiples in Peyer’s patches (lymphoid follicles)

4) Inflammatory response mediates release of prostaglandins

5) Stimulation of cyclic AMP

6) Release of fluid and electrolytes causing watery diarrhoea

Question 20

What are 2 examples of enteric fevers?

How are they initiated?

What% of patients become chronic carriers?

What are 10 clinical features of enteric fevers?

Answer 20

• 2 examples of enteric fevers:
  1) Typhoid
  2) Paratyphoid
• These fevers are systemic infections initiated in gastrointestinal tract by S. typhi or S. paratyphi
• 1-3% of patients become chronic carriers and can excrete S. typhi in faeces for several weeks after recovery
• 10 clinical features of enteric fevers:
  1) Malaise
  2) Headache
  3) Cough
  4) Rose spot rash
  5) Fever
  6) Bradycardia
  7) Severe lethargy
  8) Constipation
  9) Hepatosplenomegaly
  10) Intestinal haemorrhage

Question 21

Shigella
* Classification (3)
* Pathogenesis (2)
* Clinical presentation (3)

What type of pathogen is shigella?

What is the most important species of shigella?

How is it most often spread?

What is a severe complication?

Answer 21

• Shigella
• Classification (3)
  1) Gram negative bacilli
  2) Member of the Enterobacteriaceae
  3) Non-lactose fermenter
• Pathogenesis (2)
  1) Production of Shiga toxin (exotoxin) damages the intestinal epithelium
  2) Shiga toxin can target the glomerular endothelium causing haemolytic uremic syndrome
• Clinical presentation (3)
  1) Watery followed by bloody diarrhoea, crampy abdominal pain and fever
  2) Incubation: 1-4 days
  3) Duration of symptoms: 2-3 days
• Shigella is human-only pathogen
• S.dysenteriae is the most important species of shigella
• It is most often spread via faecal-oral route and less often by contaminated food and water
• Associated with low infectious dose
• Haemolytic uremic syndrome (HUS) is a severe complication

Question 22

Escherichia coli
* Classification (2)
* Pathogenesis (1)
* Clinical presentation (1)

What is Escherichia coli a important component of?

What do some strains possess?

How many diarrhoeagenic groups of E. coli have been described?

Answer 22

• Escherichia coli
• Classification ()
  1) Gram negative bacilli
  2) Member of Enterobacteriaceae
• Pathogenesis (1)
  1) Six different strains which cause disease by different mechanism
• Clinical presentation (1)
  1) Vary depending on strain
• Important component of gut flora
• Some strains possess virulence factors which enable them to cause infections
• Six different diarrhoeagenic groups of E. coli have been described

Question 23

Escherichia coli
* Classification ()2
* Pathogenesis (3)
* Clinical presentation (6)

What is Escherichia coli the major bacterial cause of?

Answer 23

• Escherichia coli
• Classification (2)
  1) Gram negative bacilli
  2) Member of Enterobacteriaceae
• Pathogenesis (3)
  1) Diarrhoea due to action of toxins
  2) Heat-labile (LT): structural and functional analogue of cholera toxin
  3) Heat-stable (ST): produced in addition to or instead of LT. Similar mode of action
• Clinical presentation (6)
  1) Watery diarrhoea
  2) Abdominal pain
  3) Vomiting
  4) No associated fever
  5) Incubation: 1-7 days
  6) Duration of symptoms: 2-6 days
• Escherichia coli is the major bacterial cause of diarrhoea in infants & children in developing world
• The major cause of “travellers” diarrhoea

Question 24

What is the mechanism of action of heat-labile toxin of Escherichia coli?

How is this treated?

Answer 24

• Mechanism of action of heat-labile toxin of Escherichia coli:
• Increases CAMP in the cell, causing large ion outflow from the cell, leading to dehydration of the cell
• This is treated using dehydration therapy

Question 25

Yersinia enterocolitica
* Classification (2)
* Pathogenesis (1)
* Clinical presentation (4)

What group does Yersinia enterocolitica affect?

Where can infection come from?

What pain does it mimic?

What therapy is required?

Answer 25

• Yersinia enterocolitica
• Classification (2)
  1) Gram-negative bacilli
  2) Member of Enterobacteriaceae
• Pathogenesis (1)
  1) Invades terminal ileum with inflammation of mesenteric lymph nodes
• Clinical presentation (4)
  1) Bloody diarrhoea, abdominal pain and fever
  2) Mesenteric adenitis may mimic acute appendicitis
  3) Incubation: 4-7 days
  4) Duration of symptoms: 7-14 days
• Yersinia enterocolitica mainly affects younger children
• Infection from wide range of animals including pets, undercooked pork and unpasteurised milk
• Mimics appendicitis due to right iliac fossa pain
• Only supportive therapy required – highly self-limiting

Question 26

Enterohaemorrhagic E. coli (EHEC)
* Classification (3)
* Pathogenesis (2)
* Clinical presentation (5)

Where can Enterohaemorrhagic E. coli (EHEC) be found?

What is it transmitted by?

What can be a severe complication in a few cases of Enterohaemorrhagic E. coli (EHEC) infection?

What is E.coli O157 infection the commonest cause of in the UK?

Why should we avoid antibiotics for treatment?

Answer 26

• Enterohaemorrhagic E. coli (EHEC)
• Classification (3)
  1) Gram negative bacilli
  2) Member of Enterobacteriaceae
  3) Best known as E. coli O157:H7
• Pathogenesis (2)
  1) Production of Shiga-like toxins
  2) Toxin can target the glomerular endothelium causing haemolytic uremic syndrome
• Clinical presentation (5)
  1) Bloody diarrhoea
  2) Abdominal pain
  3) Vomiting
  4) Incubation: 3-4 days
  5) Duration of symptoms: 5-10 days
• Enterohaemorrhagic E. coli (EHEC) can be found in large animal reservoirs (esp. cattle and sheep)
• It is transmitted by contaminated food, water and dairy products and direct contact with animal faeces (e.g. petting zoos)
• Haemolytic uremic syndrome (HUS) is a severe complication in 5-10% of cases
• E.coli O157 infection is the commonest cause of acute renal failure in children in the UK
• AVOID antibiotics as they promote toxin release

Question 27

What are 4 examples of gram-positive bacteria?

Answer 27

• 4 examples of gram-positive bacteria:
  1) Staphylococcus aureus
  2) Clostridium botulinum
  3) Clostridium difficile
  4) Listeria monocytogenes

Question 28

Staphylococcus aureus
* Classification (1)
* Pathogenesis (1)
* Clinical presentation (4)

What do have of Staphylococcus aureus species produce?

How is it transmitted?

At what temperature do Staphylococcus aureus bacteria multiple?

Answer 28

• Staphylococcus aureus
• Classification (1)
  1) Gram positive cocci
• Pathogenesis (1)
  1) Heat stable and acid-resistant protein toxins results in emetic disease
• Clinical presentation (4)
  1) Profuse vomiting and abdominal cramps
  2) No diarrhoea or fever
  3) Incubation: 15 minutes - 6 hours
  4) Duration of symptoms: 12 hours - 1 day
• 50% of S. aureus species produce enterotoxins
• Food (especially cooked meats and pastries) contaminated by carriers is how Staphylococcus aureus is transmitted
• Bacteria multiply at room temperature and produce toxins

Question 29

Clostridium botulinum
* Classification (1)
* Pathogenesis (2)
* Clinical presentation (3)

What are the 2 types of food related botulism?

How is Clostridium botulinum detected?

How is it treated?

Answer 29

• Clostridium botulinum
• Classification (1)
  1) Anaerobic spore-forming gram-positive bacilli
• Pathogenesis (2)
  1) Produces powerful heat-labile protein neurotoxin
  2) Absorbed toxins spread via bloodstream and enter peripheral nerves where they cause neuromuscular blockade at the synapses
• Clinical presentation (3)
  1) Neuromuscular blockade results in flaccid paralysis & progressive muscle weakness
  2) Can result in respiratory failure
  3) High mortality if untreated
• 2 types of food related botulism:
  1) Foodborne: preformed toxins in improperly processed canned foods
  2) Infant: associated with organisms germinating in gut of babies fed honey containing spores and toxins are produced in gut
• Diagnosis of Clostridium botulinum is by toxin detection
• Treatment with anti-toxin and urgent intensive supportive

Question 30

Mechanism of action of Clostridium botulinum diagram

Answer 30

Question 31

Clostridium difficile
* Classification (1)
* Pathogenesis (2)
* Clinical presentation (4)

What are Clostridium difficile spores resistant to?

What % hospitalised patients are carriers?

What is laboratory diagnosis based upon?

What are 4 control measures for Clostridium difficile?

What are 3 treatments for Clostridium difficile?

Answer 31

• Clostridium difficile
• Classification (1)
  1) Anaerobic spore-forming gram-positive bacilli
• Pathogenesis (2)
  1) Disruption of normal protective gut flora due to antibiotics, chemotherapy, or antacids
  2) Release of potent toxins (A and B)
• Clinical presentation (4)
  1) Mild to severe diarrhoea
  2) Pseudomembranous colitis
  3) Toxic colonic dilation
  4) Perforation
• Clostridium difficile spores are resistant to heat, drying, and alcohol gel
• Up to 30% of hospitalised patients are carriers
• Laboratory diagnosis based upon toxin detection
• 4 control measures for Clostridium difficile:
  1) Patient isolation
  2) Hand hygiene
  3) Use of PPE
  4) Cleaning and disinfection with bleach
• 3 treatments for Clostridium difficile:
  1) Stop precipitating antibiotics
  2) Oral metronidazole or vancomycin (severe cases)
  3) Faecal transplant (for refractory disease)

Question 32

Listeria monocytogenes
* Classification (1)
* Pathogenesis (2)
* Clinical presentation (4)

What groups is Listeria monocytogenes an important infection in?

What 3 ways is Listeria monocytogenes transmitted by contaminated foods?

Where can outbreaks occur from?

What treatment is required?

Answer 32

• Listeria monocytogenes
• Classification (1)
  1) Gram positive coccobacilli
• Pathogenesis (2)
  1) <1000 organisms may cause disease
  2) Invasive infection results in systemic spread via bloodstream
• Clinical presentation (4)
  1) Initial flu-like illness with or without diarrhoea
  2) Severe systemic infection (septicaemia/meningitis)
  3) Incubation: 14-28 days
  4) Duration of symptoms: 7-14 days
• Listeria monocytogenes is an important infection in pregnant people (with possible transplacental spread) and immunocompromised patients
• 3 ways is Listeria monocytogenes transmitted by contaminated foods:
  1) Unpasteurised milk and soft cheeses
  2) Pate and dips such as hummus
  3) Cooked meats
• Outbreaks can occur from contaminated ready to eat foods and produce
• Intravenous antibiotics (usually ampicillin and synergistic gentamicin) are required

Question 33

Helicobacter pylori (H.pylori)
* Classification (2)
* Pathogenesis (1)
* Clinical presentation (3)

How common is H. pylori infections?

How is it transmitted?

When will H. pylori infections persist?

What are 4 ways H. Pylori infection is diagnosed?

Answer 33

• Helicobacter pylori (H.pylori)
• Classification (2)
  1) Gram negative spiral shaped bacilli
  2) Urease positive
• Pathogenesis (1)
  1) Pathogenesis is complex involving cytotoxin production, and a range of factors to promote adhesion and colonisation
• Clinical presentation (3)
  1) Asymptomatic unless peptic ulceration develops
  2) Cause of 70-90% of peptic ulcers
  3) Gastric cancer risk
• H. Pylori is one of the most common infections (70% prevalence)
• Transmission by faecal-oral or oral-oral
• Infection acquired in childhood and persists lifelong unless treated
• 4 ways H. Pylori infection is diagnosed:
  1) Faecal antigen
  2) Serology testing
  3) C-urea breath test
  4) Culture from biopsy

Question 34

What are 4 factors that contribute to the pathogenesis of H. Pylori?

Answer 34

• 4 factors that contribute to the pathogenesis of H. Pylori:

1) Flagella – allows movement through viscous mucus

2) Urease – generates ammonia from urea and elevates local gastric pH

3) Adhesins – enhance binding to gastric epithelium

4) Cytotoxins – damage to gastric epithelium

Question 35

Describe the 3 medications in H. pylori Eradication Therapy

Answer 35

• 3 medications in H. pylori Eradication Therapy:
• One week therapy with a proton pump inhibitor (PPI) and two antibiotics is recommended:
  1) Omeprazole (PPI)
  2) Clarithromycin
  3) Amoxicillin (Metronidazole if penicillin allergy)