Pathogens of the GI tract

Question 1

The GI tract contains

Answer 1

Ingestion
Mouth
Oesophagus
Stomach
Small intestine
Large intestine
Egestion

Question 2

Gastroenteritis

Answer 2

Sydrome characterised by GI symptoms including

• nausea
• vomiting
• diarrhoea
• abdominal pain

Question 3

Diarrhoea

Answer 3

Abnormal faecal discharge characterised by frequent and/ or fluid stool

• associated with > fluid and electrolyte loss
• often disease of small intestine

Question 4

Dysentery

Answer 4

Abnormal inflammation of GI tract

• often blood and pus in faeces and pain, fever and abdominal cramps
• often disease of large intestine

Question 5

Enterocolitis

Answer 5

Inflammation of mucosa of small and large intestine

Question 6

Defences of mouth

Answer 6

Flow of liquids
Saliva
Lysozyme
Normal bacterial flora

Question 7

Defences of oesophagus

Answer 7

Flow of liquids

Peristalsis

Question 8

Defences of stomach

Answer 8

Gastric acid pH 1-2 provides effective barrier to most infections
Many bacteria transiently pass through stomach before infecting lower GI tract
-these must be able to resist the low pH during passage through OR take up residence if they can infect

Question 9

Defences of small intestine

Answer 9

Flow of gut contents
Peristalsis
Mucus; bile
Secretory IgA
Lymphoid tissue (Peyer's patches)
Shedding and replacement of epithelium
Normal flora

Question 10

Defences of large intestine

Answer 10

Normal flora
Peristalsis
Shedding and replication of epithelium
Mucus

Question 11

‘Food poisoning’

Answer 11

This strictly refers to ingestion of toxins or poisons in food
-e.g. bacterial toxins or heavy metals
Bacteria grow and multiply in food
Cooking kills bacteria but toxin still active - intoxication
Staphylococcus aureus
Botulism: Clostridium botulinum

Question 12

Staphylococcus aureus ‘food poisoning’

Answer 12

Growth in food after human contamination
-mainly dairy products, cooked meats, pre-packed sandwiches
50% of strains produce heat-stable enterotoxins
-also resistant to stomach acid and digestive enzymes (main route of infection from food prep, naso-pharyngeal carriage)
3-6h severe vomiting - complete recovery

Question 13

Botulism: clostridium botulinum ‘food poisoning’

Answer 13

Heat stable toxin ingested in food, leads to flaccid paralysis and death
(covered in anaerobe lecture)
Infant botulism most common

Question 14

Bacillus cereus

Answer 14

‘Fried Rice syndrome’
Self-limiting but unpleasant
Gram +ve, spore former
Some strains are harmful to humans and cause foodborne illness, while other strains can be beneficial as probiotics for animals
-spores can survive the rice cooking process, germinate and release toxins at room temp
-re-frying rice it can remain

Question 15

Gastric ulcers: helicobacter pylori

Answer 15

Previously thought to be solely ‘hurry, curry and worry’ but found to be bacterium 1983
Resistance to physical barriers - stomach acid
Produces urease
-protective cloud during transit to gastric mucin layer
-ammonia basis of breath test
Urea –urease–> ammonia + CO2
Confirmed link to gastric cancers cagA positive strain

Question 16

Infective cycle of Helicobacter pylori

Answer 16

Infects lower part of the stomach (antrum)
Causes inflammation of gastric mucosa (gastritis)
-often asymptomatic
Inflammation may lead to duodenal or gastric ulcer
-severe complications include bleeding ulcer and perforated ulcer
Duodenal ulcer and gastric ulcer –> bleeding ulcer

Question 17

Treatment for gastric ulcers

Answer 17

Now with proton-pump inhibitor PLUS metronidazole/ amoxicillin and clarithromycin

Question 18

Food-associated infections

Answer 18

Ingestion of contaminated food that contains an infectious of bacteria (>ID50)
Faecal-oral spread - wash your hands!

Question 19

Diarrhoeal treatment

Answer 19

Fluid and electrolyte replacement is essential
Antibiotic treatment often not successful and may worsen problem
-wipes out competing organisms or stimulates toxin production (C.diff)

Question 20

Diarrhoeal disease: E.coli

Answer 20

Gram -ve motile rod
Major cause of diarrhoeal disease and gastroenteritis worldwide
Complications include hemolytic-uremic syndrome (HUS)
Many genetically distinct disease causing strains
Some strains reside in normal commensal flora
Others infect urinary tract and cause meningitis
Diarrhoea: ingested in food or via faecal-oral transmission route
Genetic diversity dependent on plasmid, lysogenic phage and transposon encoded ‘pathogenicity islands’

Question 21

Lab detection of E;coli

Answer 21

Lactose fermentation: MacConkey agar
Lactose fermented on Hektoen enteric agar
PCR/ antigen tests for stereotypes

Question 22

E.coli pathogenic strains

Answer 22

EPEC
ETEC - toxin producing
EHEC - verotoxin producing
EIEC
EAEC
UPEC - causes of GU infections

Question 23

EPEC

Answer 23

Bundle-forming pili important in attachment
Type III secretion system injects proteins into host to manipulate cytoskeleton
-translocated intimin receptor (Tir)
-intimin mediates imtimate attachment to epithelial cells
Attaching and effacing lesion
Leads to watery diarrhoea

Question 24

ETEC

Answer 24

Attach via adhesive pili
Produce Heat Stable (ST) and Labile (LT) enterotoxins (cholera like) that cause diarrhoea
Common cause of travellers diarrhoea OR Delhi Belly
-no blood
-cholera like in some cases

Question 25

EIEC

Answer 25

Invade and destroy epithelial cells | Bloody diarrhoea

Question 26

EHEC (sometimes called STEC) | -look at diagram

Answer 26

Attachment similar to EPEC - pedestals Produce vero-toxin (also called Shigella-like toxin) - STx STx (verotoxin) is a potent diarrhoeal toxin (and has receptor on kidney cells) acts via damaging cells directly EHEC infections also cause haemorrhagic colitis --> bleeding --> spread to kidneys Can lead to HUS??

Question 27

HUS

Answer 27

This may lead to kidney failure (15% cases) | O157:H7 strain most well known

Question 28

Shigella (should really be classified as an E.coli)

Answer 28

Shiga toxin producing (similar to EHEC) Shigella dysenteriae -bacillary dysentry, bloody stools Shigella sonnei and flexneri -milder forms -low infectious dose 10-100 cells - sometimes ID50 Non-lactose fermenters (Maconkey agar, Hektoen enteric - green no H2S) Common in poorer countries Spread faecal-orally, often via water contamination

Question 29

Salmonella

Answer 29

Historically most common food-associated pathogen in UK Spread from food - mainly chicken and dairy products, but also person to person Invade M-cells then spread to surrounding epithelium Usually a severe but self-limiting diarrhoea and enterocolitis

Question 30

Salmonella enterica subspecies cause uncomplicated diarrhoea

Answer 30

typhimurium | enteritidis

Question 31

Lab detection of salmonella

Answer 31

MacConkey agar -non-lactose fermenter (yellow) H2S deposits on Hektoen enteric agar

Question 32

S. typhi

Answer 32

Cause of typhoid fever Infection initiates in the intestine Spreads systemically- transported in macrophages around body Seed many organs before further spread Causes increasing fever over 14 days >> GI symptoms Pre-antibiotics 12-16% died Complications: GI lesions and haemorrhage Toxaemia- endocarditis Meningitis Vi antigen vaccine recommended for travel 1 – 3 % become carriers >> gall-bladder

Question 33

Number one cause of food poisoning in UK

Answer 33

Campylobacter spp.

Question 34

Campylobacter spp.

Answer 34

Gram-negative micro-aerophiles Campylobacter jejuni most common Acquired by ingestion of contaminated food Major reservoir in Chickens> 75% of all we buy have colonisation Symptoms like Shigellosis and Salmonellosis: -ulceration (jejunum), diarrhoea -up to 10 movements per day… - longer lasting illness- up to 3 weeks! -complications: Guillame Barre and reactive arthiritis

Question 35

Cholera (biggest historical GI bug)

Answer 35

Caused by motile gram -ve comma-shaped bacterium Cause of 8 recorded worldwide pandemics since 1817 O1 serotype most important historically: classical and El Tor (modern) ~1.3-4 million cholera cases and 21000–140,000 deaths due to cholera every year- mainly developing countries

Question 36

Cholera mechanism of infection

Answer 36

Vibrio ingested in large numbers -can survive in fresh and sea-water -possible marine invertebrate reservoir -infectious dose >10^8 Sensitive to stomach acid -large dose needed to cause disease unless pt achlorhydric or taking antacids -in these cases infectious dose drops >10^5 Colonization of small intestine depends on motility (polar flagella) production of mucinase attachment to specific receptors --> toxin production Massive loss of fluid and electrolytes -no damage to enterocytes; no blood or WBC in stool

Question 37

Normal water flow in gut vs cholera toxin

Answer 37

Normal: net-flow of water is from lumen into tissue + cholera toxin -ADP-ribosylation of G-protein signalling pathways causes increased secretion of Chloride ions -this prevents influx of Sodium ions into cells -results in rapid loss of water from tissue- massive diarrhoea This rapid fluid loss results in loss of 1-2 litres of fluid per hour in full-blown cases Rapid fluid and electolyte replacement required or dehydration and death result Characteristic rice-water stool No tissue damage, all symptoms due to massive fluid loss

Question 38

Symptoms of cholera: no dehydration

Answer 38

``` Well, alert Normal eyes Tears present Moist mouth and tongue Drinks normally, not thirsty Skin pinch goes back quickly ```

Question 39

Symptoms of cholera: severe dehydration

Answer 39

``` Lethargic or unconscious; floppy Very sunken and dry eyes Absent tears Very dry mouth and tongue Drinks poorly or not able to drink Skin pinch goes back very slowly ```

Question 40

Prevention of cholera

Answer 40

Vaccines have been unsuccessful but several available with only temporary immunity gained -WHO trialling 2 vaccines currently with protection 6m-2y Best prevention method is improvement of water system and sanitation -hard to get aid for that, especially in war-torn/ lawless regions

Question 41

Viral causes of GI infections

Answer 41

Of the 3 million infants that die from gastroenteritis 20% are viral sources Major problem in developing countries Children may have 60 days of diarrhoea per year – major effect on growth and nutrition Mainly oral-fecal Very hard to identify non-bacterial cases Not until 1972 were viruses isolated from faeces

Question 42

Rotaviruses

Answer 42

``` Wheel-like viral particle Diarrhoea caused by tissue damage in small intestine Dehydration main risk Very low-infectious dose Very contagious V resistant to celaining products ```

Question 43

Winter vomiting virus

Answer 43

Norovirus (Norwalk viruses) - not cultivated Chills, headache, fever, nausea, vomiting, v-low infectious doses (10) Recovery in 24 – 48 hours Common in hospital settings, Hard to clean away