GIT infections Part A

Question 1

What are the most common GIT infections and what are some of the defences of the GIT? Also what are some of the GIT infection types?

Digestive system = major portal of entry

Answer 1

Resource poor countries: Vibrio cholerae, E.coli (common harmless intestinal organsim, some strains cause disease)

Resource rich country: Salmonella, Shigella and Campylobacter;E.coli in travellers diarrhoea

GIT defences

• Every day large amounts of microbes are swallowed
• Body’s defence systems are very effective and kill/remove/inactivate

> Mouth = saliva

> Oesophagus = peristalsis

> Stomach = acid pH

> small intestine = mucus, bile, peristalsis

> large intestine = persitalsis, mucus, flora

Git infection Types

GIT infections grouped into: remain localised in gut –> invade beyond gut and infect other sites

Transmission –> pathogens need to be excreted in large numbers into environment to survive to infect new host

> Through contamination of food/water

Question 2

Symptoms of enteric infections? How to classify enteric infections?

Answer 2

Most common symptoms are:

• Diarrhoea – the most common symptom
• Fever, vomiting, abdominal pain

The nature of the diarrhoea is used to classify enteric infections into three categories

1. Water diarrhoea: usually enterotoxin producting organisms

> significant fluid loss but only lasts 1-3 days

2. Dysentery: invasive and toxin proucing organisms

> less diarrhoea but may contain blood and pus (3-7 days)

3. Enteric fever: invasive organsims which produce bacteraemia

> cnan be systemic and fatal, lasting for a week or longer

Question 3

Enterobacteriaceae = Gram negative rodes –> some can cause enteric disease

> pathogens produce exotoxins

There are three type: E.coli, Salmonella, Shigella

DESCRIBE THE GENERAL CLINICAL FEATURES OF DIFFERENT MANIFESTATIONS OF E.COLI

Answer 3

• Aerobic/facultative anaerobe – Gram-negative, rod
• Most predominant organism of the large intestine – Approx. 10^{7 -} 10⁹ /g of faeces.
• Used as an indicator of faecal contamination:

> Coliforms – used to detect faecal contamination in food/water or products, not necessarily pathogenic

>Indicate that there may be other, pathogenic microbes present that are harder to detect

• Classified according to O (cell wall), K (capsule), H (flagella) antigens
• Many strains use pili to attach to host cells

Clinical Significance of E.coli infections

• Ordinarily non-pathogenic – harmless gut organisms –> May be opportunistic in some circumstances

Some strains are true pathogens – contain virulence factors

• Major cause of urinary tract infections (85%)
• Primary pneumonia
• Major cause of neonatal meningitis
• Wound infections and peritonitis (sepsis)

Gastroenteritis

• Common cause of travellers diarrhoea
• Treatment = antibiotic therapy is not an indication for E.coli diarrhoea
• Supportive therapy = fluid replacement

Question 4

Enterobacteriaceae = Gram negative rodes –> some can cause enteric disease

> pathogens produce exotoxins

There are three type: E.coli, Salmonella, Shigella

DESCRIBE THE GENERAL CLINICAL FEATURES OF DIFFERENT MANIFESTATIONS OF Salmonella

Answer 4

• Small, Gram-negative bacillus – usually motile
• All types of Salmonella are now classified into two species (DNA sequence): S. enterica cause disease in warm blooded animals, including humans
• Salmonella bongori – restricted to cold-blooded animals

Salmonella enterica

• Salmonella invade the gastrointestinal tract tissue but don’t produce exotoxins
• Some strains can invade further and cause systemic disease
• Over 2,000 S. enterica serotypes; most do not cause disease but some are significant pathogens
• Classified according to O (cell wall) and H (flagella) antigens

Salmonella Infection** **(4 groups)

Gastroenteritis (localised to the gut) –> most common form

Bacteraemia (acute gastroenteritis and spread to other sites) –> less common (only a few strains)

Enteric fever (bacteria spread and involve multiple organs) –> can last for weeks if untreated

Typhoid fever (more severe form of enteric fever) –> caused by salmonella typh

Salmonella Pathogenesis (gastroenteritis)

• Bacteria adhere to and induce host cells to internalize them
• cross the epithelial layer and then into sub-epithelial tissue
• Salmonella are quite resistant to phagocytosis
• Host immune cells generally confine infection to GI tract
• Diarrhoea occurs
• 2-5 days

Salmonella pathogenesis (enteric fever)

• Bacteria adhere and invade
• Bacteria can survive in macrophages and dendritic cells and infect local lympatic system –> then travels systemically
• Transported in infected cells to liver, spleen, bone marrow
• Bacteraemia can occur in 2 weeks as organisms re-enter blood

Salmonella pathogenesis (typhoid fever)

• Typhoid fever = most severe form of enteric fever caused by salmonella enterica serovar typhi (salmonella typhi)
• Similar to enteric fever except symptoms are more severe and disease is much more likely to be lethal
• cause of morbidity and mortality (typhoid mary)

SALMONELLA TREATMENT

• Supportive therapy (main treatment) –> replacement of fluids and electrolytes
• Antibiotics not generally used for gastroenteritis but are useful in treatment of enteric fever (systemic infection)
• Vaccines - for travellers to endemic regions

Question 5

What is Shigella? Discuss clinical features and pathogenesis of the disease caused by major strains?

Answer 5

• Shigella are non-motile (no H antigens= flagella),
• Gram-negative rods
• Cause bacillary dysentery (inflammation of intestine which results in severe diarrhoea) in humans
• Invasive and toxigenic infection - mucosal ulcerations
• Habitat is almost exclusively human gut
• Major species: Shigella dysenteriae = most severe disease

Shigella - Clinical Features

• Symptoms range from none to servere bacillary dysentery
• Two stage disease

1. Initial non-invasive colonisation and toxin production (watery diarrhoea due to enterotoxic activity of shiga toxin)
2. Second stage invasion damage of large intestine epithelium (severity enhances by cytotoxic activity of shiga toxin)

>Typical symptoms of dysentery with frequency small stools with blood and mucus, cramps, fever

Shigella Exotoxin: Shiga Toxin

• Shiga toxin is neurotoxic, cytotoxic and enterotoxic
• enterotoxic effect: binds to intestinal epithelial receptors and causes chaos
• cytotoxic effect: inactivates the 60s ribosomal subunit (inhibits protein synthesis causing cell death )
• neurotoxic effect: fever and abdominal cramping

Question 6

What is cholera? Discuss clinical features and pathogenesis of disease caused by the major strains

Answer 6

Causative organism: Vibrio cholerae

• Comma-shaped, motile, Gram-negative rod
• Salt tolerant
• Found in fresh and salt water and seafood, free-living
• Produces a potent enterotoxin
• Most is asymptomatic (asymptomatic people could be carriers)

Clinical Features

• Transmission by faecal-oral route
• > From contaminated water and food, seafood
• 1-4 days incubation period

Copious volumes of watery diarrhoea – the characteristic “Rice water stools”.

• Dehydration, electrolyte imbalance, acidosis, circulatory collapse and possible eventual death

Treatment = intensive fluid replacement therapy

Identification

• Cholera strains are identified on the basis of different structures of O antigens (cell wall: LPS)

Pathogenesis

• The organism colonises the intestine but does not invade
• Produce enterotoxin
• Enterotoxin is composed of 1x A and 5x B sub-units.
• B-sub unit targets the toxin to the ciliated epithelial cell in the gut
• Inside the cell = A sub-unit causes activation of adenylate cyclase (leads to increase cAMP –> causes diarrhoea and dehydration)

Vaccine

• Cholera is not common and vaccination not recommended
• For travellers to areas where cholera is endemic, there is one vaccine –> Dukoral Oral Inactivated Vaccine (killed vaccine)

Question 7

What is Campylobacter? Discuss it pathogenesis

Answer 7

• Small, curved, s-shaped or spiral rods
• Gram-negative
• Motile, sometimes microaerophilic.
• Two common species, C. jejuni and C. coli cause mild to severe diarrhoeal disease
• C. jejuni is a major cause of foodborne illness causing acute bacterial enteritis worldwide
• Poultry are an important source of infections with this organism – in poultry Campylobacter are commensal organisms

Campylobacter Pathogenesis

• The main symptom is diarrhoea and also associated abdominal pain (vomiting is uncommon)
• invasive bacteria –> lead to colitis (invade by endocytosis and produce cytotoxin)
• Treatment: antibiotics

Question 8

What is H.pylori

Answer 8

Very common organism which colonises the stomach ▪

• up to 40% adults
• Causes a chronic low level inflammation of gastric epithelia
• Associated with 90% duodenal ulcers and 70- 80% gastric ulcers
• Also associated with gastric cancer
• Special mechanisms allow it to survive the acid environment e.g. urease enzyme which helps neutralise pH
• Current research suggests non-pathogenic H. pylori strains may have a beneficial effect

Question 9

What is clostridum difficile

Answer 9

• Imbalance of normal gut bacteria can enable growth of C.difficile
• Gram-positive rod
• C.difficile causes diarrhoea and colitis following antibiotic therapy
• Normally controlled by the normal flora of gut​
• Antibiotics kill the normal flora and C. difficile is able to thrive
• Bacteria produce toxins which damage epithelium
• This is a significant hospital acquired infection

Question 10

How does food poisoning work?

Answer 10

• Bacteria contaminate food and produce toxins which are consumed with the food – bacteria don’t actually infect host
• S. aureus

> Many strains produce an enterotoxin which is quite stable

> Cooking may kill bacteria but not inactivate toxin

>Acts on CNS to trigger severe vomiting (no diarrhoea)

• Botulism – Clostridium botulinum (also see CNS lecture)

>Environmental organism

>Rare disease but toxin causes serious consequences as they block neurotransmission – paralysis

>Inadequate cooking or food storage