0318 - Infectious Diarrhoea II

Question 1

What are the three ways by which enteric bacteria can cause diarrhoea?

Answer 1

Increased secretion or decreased absorption of fluids and electrolytes (SECRETORY)

Loss of absorptive surface, increasing osmolarity of contents, and malabsorption (OSMOTIC)
Inflammation resulting in fluid exudation (INFLAMMATORY)

Question 2

How can you identify inflammatory diarrhoea? What infection can cause it?

Answer 2

Fever and neutrophils (pus) in stool.

Can be caused by any intracellular pathogen.

Question 3

List at least 3 intracellular pathogens that cause infectious diarrhoea

Answer 3

Shigella

Enteroinvasive E Coli

Salmonella enteritidis

Campylobacter

Listeria monocytogenes

Question 4

Describe Shigella

Answer 4

Non-motile, Gram-negative rod. Facultative anaerobe resistant to gastric acid and bile salts (small infective dose).

No animal reservoirs, not found in the environment.

Faecal-oral spread, flies acts as vector.

Causes shigellosis

Question 5

How can shigella be differentiated from salmonella?

Answer 5

Inability to ferment xylose - they will show up as different colours when incubated on XLD agar (shigella - red, salmonella black)

Question 6

What is enteroinvasive E. Coli (EIEC)?

Answer 6

Nearly identical to shigella, and causes shigellosis in the same way.

Question 7

What is Shigellosis?

Answer 7

Paediatric Disease in developing countries, caused by Shigella or EIEC

Incubation 1-4 days, duration 2-3 days

Small infective dose (10-100 organisms)

Epidemics occur due to overcrowding/poor sanitation, and re-infection is possible
Fever, abdo cramps, severe bloody diarrhoea often with pus and mucous.

Question 8

Describe Salmonella

Answer 8

Motile, Gram-negative rods. Facultative anaerobes, resistant to bile salts but not stomach acid.

Grow optimally at 37, but any temperature <54

Pathogenic subspp are S. Enterica enterica.

Question 9

What are the two broad classification of Salmonella Enterica?

Answer 9

Non-typhoidal and typhoidal

Question 10

Briefly outline non-typhoidal salmonella enterica.

Answer 10

Non-typhoidal - cause acute gastro. S. enterica typhimurium and S. enterica enteritidis. Large animal reservoir - transmitted via food.

High infectious dose, causes watery diarrhoea with pus, usually self-limiting.

Question 11

Briefly outline typhoidal salmonella enterica.

Answer 11

Typhoidal - cause typhoid/paratyphoid/enteric fever. S. Enterica Typhi and S enterica paratyphi. Faecal-oral route, and S. enterica typhi associated with asymptomatic carriage. Only human hosts.

Low infectious dose, causes pussy diarrhoea, with fever, headache, nausea, sometimes rash.

Treated with antibiotics..

Question 12

Describe campylobacter

Answer 12

Motile, Gram-negative comma-shaped rods

Thermophilic (42 degrees optimal)

Microearophilic (5-7% O2)

Question 13

How does shigella cause shigellosis?

Think virulence factors/mechanisms

Answer 13

Can lyse the phagosome to replicate in the cytoplasm (including in macrophages).

Has number of toxins (e.g. Shiga, SigA) and a type III secretion system.

3 mechanisms for causing diarrhoea - Inflammatory (due to invasion), osmotic (loss of absorptive surface), and secretory (due to enterotoxins)

IcsA autotransporter most important virulence factor.

Question 14

What is IcsA? Why is it important?

Answer 14

Most important virulence factor for shigella. Allows intercellular spread.
Recruits host cell actin, and polymerises it into a comet tail, allowing it to ‘shoot’ into neighbouring cells.

Question 15

What are the virulence strategies for salmonella?

Answer 15

Invasion, with a type III secretion system and effector proteins required for invasion and replication in both epithelium and macrophages.

LT-like (AB5) toxin, and other enterotoxins.

S. Enterica Typhi has a capsule.

Question 16

What is the course of a typical typhoidal salmonella systemic infection?

Answer 16

Organism consumed

Exit small intestine via M cells

Taken up by macrophages and multiplies in mesenteric lymph nodes.

Released into bloodstream (primary bacteraemia)

Removed from blood by macrophages in spleen, bone marrow, liver, multiply and re-enter bloodstream (secondary bacteraemia, symptoms develop)

Re-enter GIT via gall bladder, causing inflammation, ulceration, and necrosis.

Question 17

What are the virulence strategies for Campylobacter?

Answer 17

Invasiveness (intracellular)

Capsule important for virulence, adherence, and invasion, along with lipooligosaccharide (LOS)

Flagellum required for colonisation, virulence, and invasion - also acts as a secretion apparatus for invasion antigens.

Cytolethal distending toxin can cause DNA damage.

Question 18

Describe Listeria monocytogenes.

Answer 18

Motile, Gram-positive rod

Widespread in the environment.

Low infectious dose

Optimal growth at 37, but psychotroph (2-4 degrees)

Opportunistic pathogen.

Question 19

What are the virulence strategies for listeria monocytogenes?

Answer 19

Invasiveness - similar to shigella, including intercellular spread, and ability to lyse phagosome to replicate in the cytoplasm (in this case via listeriolysin O)

ActA provides comet tail for intercellular spread.

Sensory - increased temperature and low pH produces certain virulence factors. Production of Listeriolysin O and ActA is triggered by low-iron intracellular environment.

Question 20

What is the source of campylobacter?

Answer 20

Common GIT commensal of chickens and many other animals (cattle, pigs, wild birds). Particularly found in contaminated chicken and unpasteurised milk.

Question 21

Summary

Answer 21

3 clinical mechanisms of diarrhoea - inflammatory, osmotic, secretory.

Intracellular pathogens invade host cells and proliferate inside them. This lecture covered Gram-negative Rods (shigella, campylobacter) and listeria, which is Gram Positive.

Intracellular enteric pathogens invade and proliferate inside intestinal epithelium, and sometimes macrophages to cause infectious diarrhoea, and potentially systemic disease.

Many of these pathogens are normal flora in other animals.