This document discusses gastrointestinal tract infections. It notes that diarrheal diseases are among the top causes of death globally, with over 1.7 billion cases of childhood diarrheal disease annually. It provides information on the pathogenesis of gastrointestinal infections, including the roles of enterotoxins, invasion, cytotoxins, attachment, and preformed toxins. Examples are given of specific microorganisms that cause infection via each of these mechanisms. The document also covers topics like laboratory diagnosis, clinical manifestations in different settings, and therapeutic approaches.

1. Gastrointestinal tract infections

2. Anatomy

3. Global public health problem
• Diarrheal diseases are
the 9. leading cause of
death.
• 1.7 billion cases of
childhood diarrheal
diseases.
• Although acute
diarrheal syndromes are
usually self-limited,
some patients with
infectious diarrhea
require diagnostic
studies and treatment.
Deaths from Diarrhoeal diseases in 2012 per million persons. Statistics from WHO

4. Pathogenesis
• Host factors
• acidity of the stomach
• normal peristalsis
• Peyer’s patches (macrophages, B cells, T cells)
• secretory IgA
• personal hygiene
• age
• NORMAL MICROBIOTA !!!
• Antibiotic associated colitis
• Pseudomembranosus colitis

5. Examples of Microorganisms That
Causes GIT Infection for Each
Pathogenic Mechanism
Mechanism
Examples of
Microorganisms
Enterotoxin
Vibrio cholerae, Enterotoxigenic E. coli,
Clostridioides difficile, Aeromonas spp.,
Campylobacter jejuni
Invasion
Shigella spp., Enteroinvasive E. coli,
Campylobacter jejuni, Salmonella spp.,
Plesiomonas shigelloides, Yersinia
enterocolitica, Edwardsiella tarda
Cytotoxin
Shigella dysenteriae, Clostridioides difficile,
Enterohemorrhagic E. coli
Attachment within or close to
mucosal cells
Enteropathogenic E. coli, Enterohemorrhagic
E. coli
Preformed toxins S. aureus, C. botulinum, Bacillus cereus

6. Enterotoxins
• Alter the metabolic activity of intestinal epithelial
cells.
• Primarily in the jejunum and upper ileum.
• There are NO blood and polymorphonuclear
cells in stool !!!

7. Invasion
• After initial and essential adherence to GI mucosal
cells, some enteric pathogens can gain access to the
intracellular environment. Invasion allows the
organism to reach deeper tissues, access
nutrients for growth, and possibly avoid the host
immune system.

8. Shigella related stool sample
with PMC

9. Cytotoxins
• Disrupt the structure of individual intestinal
epithelial cells.
• Strong inflammatory response.
• Numerous polymorphonuclear neutrophils and
blood in stool sample !!!
• Dysenteryform!
The toxin targets the globotriaosylceramide
receptor; becomes internalized and
transported into the ER. The is then able to
cleave the 28S ribosomal ribonucleic acid
interfering with protein synthesis. The
ultimate effect is vascular damage, bloody
diarrhea, and potentially HUS.
C. difficile toxigenic strains produce two
exotoxins; toxin A and toxin B. Both toxins
bind to receptors on the brush border of the
intestinal epithelium and internalized. Toxin
A: enterotoxin. Toxin B: cytotoxin, modifies
the actin cytoskeleton. This affects
polymerization, causing disturbances and
separation of the tight junctions.

10. Attachement
• Certain strains of E. coli referred to as the
enteropathogenic E. coli (EPEC) attach and then
adhere to the intestinal brush border. This localized
adherence is mediated by the production of pili.
EPEC disrupts normal cell function by effacing the
brush border of epithelium, thereby causing
diarrheal disease. This complete process is referred
to as attachment and effacement.

11. Preformed
toxins
• Produce their toxins in foodstuffs before they are
ingested; preformed toxin.
• Intoxications
• Particularly in staphylococcal food poisoning
and botulism!

12. Types of Enteric Infections
Mechanism Symptoms Examples
Upsetting of fluid and
electrolyte balance
Watery diarrhea
No fecal leukocyte
No fever
Vibrio cholerae,
Enterotoxigenic E. coli,
Bacillus cereus
Invasion and possible
cytotoxin production
Dysenteriform diarrhea
Fever
Fecal leukocytes
Shigella spp., Salmonella
spp., Enteroinvasive E. coli
Penetration with
subsequent acces to the
bloodstream
Signs of systemic infection
Fever
Salmonella enterica serotype
Typhi
Yersinia enterocolitica

13. Clinical manifestations
• Institutional settings
• Diarrheal illness can be a major
problem in institutional settings
such as daycare centers,
hospitals, and nursing homes.
• C. difficile is a major enteric
pathogen that has been identified
in outbreaks in hospitals and
other settings.
• Sudden onset of watery/bloody
diarrhea and abdominal cramps
during antibiotic therapy.

14. Clinical manifestations
• Traveler’s Diarrhea
• Individuals who travel into
developing geographic areas at
particularly high risk for
developing diarrhea. In areas
with poor sanitation, enteric
pathogens heavily contaminate
the water and food. Although
many types of enteric pathogens
can cause diarrhea in travelers,
ETEC is a leading cause.

15. Clinical manifestations
Foodborne and Waterborne Gastrointestinal Syndromes
General symptoms Incubation Examples
Nausea and vomitting 1-8 hours S. aureus, B. cereus
Abdominal cramps and
diarrhea
8-16 hours C. perfringens, B. cereus
Fever, cramps and diarrhea 6-48 hours
Salmonella spp, Shigella spp,
Campylobacter spp, EIEC, Y.
enterocolitica
Cramps, watery diarrhea 16-72 hours
L. monocytogenes, ETEC,
Vibrio cholerae
Fever, cramps without
diarrhea
1-11 days Y. enterocolitica
Bloody diarrhea with low
fever
3-8 days EHEC
Paralysis 18-36 hours C. botulinum
Systemic illness S. typhi, S. paratyphi

16. Clinical manifestations
• Gastritis refers to
inflammation of the gastric
mucosa. This illness is
associated with nausea and
upper abdominal pain;
vomiting, burping, and
fever may also be present.
A curved organism called
Helicobacter pylori is seen
on the surface of gastric
epithelial cells of patients
with gastritis.

17. Salmonellosis
Strictly human
adapted
S. typhi
S. paratyphi A, B,C
Broad host range
many strains, e.g.
S. typhimurium
S. enteritidis
Primarily animal adapted
certain strains
S. choleraesuis
Disease enteric fever
gastroenteritis,
septicemia in
immunocompro
mised
bacteriaemia,
Infectious dose moderate high high
Source
infected person
( Ø zoonotic!)
human &
zoonotic
zoonotic
Transmission
water, food
direct contact
food (enrichment) food(enrichment)
Prevention by
proper food
handling
+ + +
Vaccine + - -

18. Pathogenesis of Salmonella
gastroenteritis

19. Overview of E. coli that cause diarrhea
in humans
Type Pathogenesis Other
EPEC
Initially attaches in the colon and small intestine
and then becomes intimately adhered to intestinal
epithelial cells, subsequently causing the loss of
enterocyte microvilli (effacement).
Diarrhea in infants,
particularly in large
urban hospitals
ETEC
Produces LT or ST enterotoxins; LTs are closely
related in structure and function to cholera toxin;
STs result in net intestinal fluid secretion by
stimulating guanylate cyclase.
Common cause of
traveller’s diarrhea;
infects all ages
EIEC
Diarrhea results are virtually identical to those of
Shigella spp.
Very difficult to
distinguish from Shigella
spp.
EHEC
Attaches to and effaces gut epithelial cells in a
similar manner as EPEC; Shiga like toxins.
E. coli O157:H7
EAEC
Forming small clumps of bacteria on the cell
surface; a heat-stable enterotoxin, and a heat-labile
enterotoxin
Primarily young children.

21. General characteristics of Agents of Enteric
Infections

22. Cont.
Baily and Scotts’ Diagnostic microbiology, Elsevier

23. Laboratory
diagnosis
Bristol scale

24. Culturing

25. Culturing
XLD (Black vs. yellow)

26. Culturing
MacConkey (Lactose positive vs Lactose negative)

27. Culturing
CCDA (Campylobacter; dry flat grey colonies)

28. C. difficile
• As it may be a
member of the
normal flora of the
gut, culture alone
is not conclusive.
• The point is to
detect TOXIN
PRODUCTION!
Test Advantage Diasadvantage
Glutamate-
dehydrogenase
enzyme
immunoassay
Fast, high
sensitivity
Alone is not
predictive, toxin
detection is also
needed
Toxin A/B enzyme
immunoassay
Fast, medium
specificity
Moderate
sensitivity
Culturing High sensitivity Long turnaround
time
Cell cultures
(cytotoxicity assay)
High sensitivity Long turnaround
time
Nucleic acid-based
detection
Fast, High
sensitivity
Expensive, the
problem of
colonization

29. Multiplex PCR-based diagnosis
One Hour !!!

30. Therapeutic
approaches
Resting and
drinking plenty of
fluids !!!

31. Aeromonas species - use cefixime and most third-generation and fourth-generation
cephalosporins.
Bacillus species - no antibiotics, but vancomycin and clindamycin are first-line drugs
for severe disease.
Campylobacter species - Macrolides may shorten the illness duration and shedding.
C. difficile - discontinue potential causative antibiotics; use oral metronidazole or
vancomycin (fidaxomicin – sporulation inhibition)
C. perfringens - do not treat with antibiotics
Listeria species - no antibiotics; ampicillin is first-line drugs for invasive disease
Plesiomonas species - trimethoprim-sulfamethoxazole or any cephalosporin
V. cholerae - tetracycline
Yersinia species - trimethoprim-sulfamethoxazole, fluoroquinolones, aminoglycosides

32. Further therapeutic comments
• E. coli
• Antibiotic treatment appears to increase the likelihood of developing
HUS. Sumetrolim is a first-line drug, but a parenteral second-generation or
third-generation cephalosporin for systemic complications should be used.
• Salmonella/Shigella species
• Antibiotic treatment prolongs the carrier state and is associated with
relapse.
• Ampicillin is recommended for drug-sensitive strains. Trimethoprim-
sulfamethoxazole, fluoroquinolones, or third-generation cephalosporins.