goodEach part of the DS has special defense mechanisms that protect it from pathogenic microorganisms Every day we swallow large numbers of microorganisms b/c of the body's defense mechanisms, however, they rarely succeed in surviving the passage to the intestine in sufficient numbers to cause infection and most important acts as a physical barrier making difficult for bacteria to access the epithelial cell surfaces coats the bacteria, making it easier to remove via peristalsis

1. Microbiology of the
Digestive System (DS)
1

2. Learning Objectives:
o To describe DS immunology
o To list the common pathogens
that infect the DS
o To discuss the common:
 Bacterial infections of the DS
 Viral infections of the DS
2

3. Lecture outline
 Overview
 1. Immunology of the DS
 2. Infections of the DS:
o A. List of common pathogens of the DS
o B. Major pathogens of the mouth
o C. Major pathogens of the stomach
o D. Major pathogens of the intestine
and/or liver:
1. Major Bacterial Pathogens
1.1. Campylobacter jejuni 1.4. Shigella species
1.2. Vibrio cholera 1.5. Salmonella species
1.3. Esherichia coli 1.6. Clostridium difficile
2. Major Viral pathogens
2.1. Rota virus
2.2. Hepatitis virus
3

4. Overview: Structures of the Digestive System
- GIT(GUT)= pathway form mouth to anus
- Accessory digestive organs

5. 1. Immunology of the DS
o Each part of the DS has special defense
mechanisms that protect it from pathogenic
microorganisms
 Every day we swallow large numbers of
microorganisms
 b/c of the body's defense mechanisms,
however, they rarely succeed in surviving
the passage to the intestine in sufficient
numbers to cause infection.
5

6. Immunology of the DS…
1. Perstalisis
o Prevent microbial colonization
2. Mucosal epithelium
o Provides mechanical barrier
o Lines all parts of the GIS
3. Mucus
o acts as a physical barrier
o making difficult for bacteria to
access the epithelial cell surfaces
o coats the bacteria, making it easier
to remove via peristalsis
6

7. Immunology of the DS…
4. Glycocalyx
o a glycoprotein & polysaccharide
layer that covers the surface of
the epithelial cells
o prevents pathogens from attaching
to the epithelial cells
o serves as a chemical trap that binds
microorganisms of the normal flora
5. Stomach acidity
o Parietal cells produce HCl
o The pH of the stomach is ~2 that
kills most ingested microbes 7

8. Immunology of the DS…
6. Bile
o Solubilizes lipids, inactivates
& prevents microbial grow
- enveloped viruses are inactivated
- many bacteria are unable to grow
at a high bile salt concentration
7. Secretary IgA
o Helps prevent colonization by
pathogens
8. Payer patches
o Provide a homing site for
lymphocytes
8

9. Immunology of the DS…
9. Normal flora defend the body by:
o Competing with pathogens:
- for nutrients & epithelial cell
receptor sites
o Production of antimicrobial factors
such as; bacteriocins & lactic acid
N.B. :- All components of the GIT
except esophagus & stomach
possess normal flora
:- esophagus & stomach are
almost free of microbes
Why?
9

10. 2. Infections of the DS
o When pathogenic microorganisms or their
toxins breach these defense mechanisms,
disease can occur
i.e. Pathogenic microorganisms cause
GIT disease either:
- by invasion of the GIT mucosa or
- by toxin release in the GIT or
food intoxication
o Infections of the gastrointestinal tract
can be grouped into :
 those that remain localized in the gut and
 those that invade beyond the gut to cause
infection in other sites of the body. 10

11. A. List of common pathogens of the DS
Pathogen Disease Site Affected
1. Bacterial pathogens
- Streptococcus mutans Dental caries (tooth decay) Mouth (Teeth)
- Helicobacter pylori Gastritis, PUD Stomach & Duodenum
- Cambilobacter jejeni Diarrhea, Dysentery Small Intestine + colon
- E. coli pathogenic strains Diarrhea &/or dysentery Small Intestine + colon
- Vibrio cholera Cholera Small Intestine
- Shigella species Diarrhea &/or dysentery Small Intestine
- Salmonella typhi Typhoid fever (an enteric fever) Small Intestine, liver
- Salmonella paratyhi A Paratyphoid fever (enteric fever) Small Intestine, liver
- Clostridium botulinum Diarrhea due to its preformed toxin Colon
- Clostridium perfringens “ “ “ Colon
- Staphylococcus aureus “ “ “ Small Intestine
- Bacillus cerus “ “ “ Colon
- Clostridium difficile Antibiotic associated diarrhea Colon
11

12. List of common pathogens of the DS…
Pathogen Disease Site Affected
2. Viral pathogens
- Mumps virus Parotitis (swelling of
the parotid glands
Mouth (salivary
gland)
- Rotavirus Diarrhea Small Intestine
- Astrovirus Diarrhea Small Intestine
- Norovirus Diarrhea Small Intestine
- Hepatitis A - E Hepatitis Liver
3. Fungal pathogens
- Candida albicans Oral thrush, Esophagitis Mouth, Esophagus
12

13. B. Major pathogens of the mouth
1. Streptococcus mutans
- Cause dental caries
Properties Epidemiology & Pathogenesis Laboratory Dx Management
- Are gram
+ve bacteria
- Are cocci
shaped &
arranged in
chain
- Are catalase
negative
- Are
fastidious
organisms
- Have no
Lancefield
classification
- Belong to
viridans
group
- Normal flora of the oral cavity
- RF: Poor oral hygiene
- Dental caries is a chronic
infection of enamel or dentine
due to bacteria normally found
in the mouth
Pathogenesis:
• S. mutans produces dextran
(insoluble & sticky polysacharide)
from sucrose
• A biofilm containing high numbers
of Streptococcus mutans forms
on the surface of the tooth.
• The bacteria in the plaque break
down sugar in the saliva and
produce acid that damages the
enamel of the tooth
• and eventually forms a cavity on
the surface of the tooth.
- Specimen: Throat
swab
- Microscopy:
Gm +ve cocci
in chain
- Culture:
Alpha or gamma
hemolytic on
blood agar
- Biochemical test
Optochin resistant,
Bile not soluble
To prevent
dental caries:
- patients should
be encouraged
to brush and
floss their teeth
daily and
- avoid sweet
and sticky
foods.
13

14. 2. Mumps virus
- Belong to paramyxoviridae
- Primarily cause parotitis
Parotitis = painful swelling of the salivary glands
Properties and
Epidemiology
Pathogenesis & Clinical
manifestations
Laboratory Dx Management
 Properties
- It has SS (-) RNA
genom
- It has helical capsid
symmetry
- It is enveloped virus
- It replicates in host
cytoplasm
- Immunity is life long
 Epidemiology
- MT: Inhalation of large
dropplet aerosol
- RH: only human
- GD: world wide
- RGs:- unvaccinated &
immunocmpromised
people
N.B. crowding favors
 Pathogenesis:
• Virus infects epithelial cells
of respiratory tract.
• It results in viremia then
Infects parotid gland
• causes lysis of cells that
resulting in inflammation
• It causes marked swelling
of the parotid gland
• Principal symptom is
swelling of parotid
• Cell-mediated immunity is
essential for control of
infection and responsible
for causing some of the
symptoms.
• Antibody is not sufficient
because of virus’s ability to
 Specimen:
- Saliva, and
secretions from
parotid duct
 Culture:
- Mumps virus
grows well in
monkey kidney cells
 Serologic test
- helps to detect
mumps virus
antigen &
antibody
 Molecular tests
example RT-PCR
- helps to detect
viral genome
 Treatment
- There is no
specific
therapy
 Prevention
• Live
attenuated
vaccine is part
of measles-
mumps rubella
vaccine.
14

15. C. Major pathogen of the stomach
1. Helicobacter pylori
(H. pylori)
 Diseases:- Gastritis & PUD
:- Gastric adenocarcinoma
:- Gastric MALT lymphoma
 General property:
 It is spiral or S shaped Gm –ve rods
 It is catalase, oxidase, & urease +ve
 It is motile with multiple polar
flagella (corkscrew motility)
 It is microaerophilic & fastidious
 It is a slow growing bacterium 15

16. Epidemiology
 GD: World wide in distribution
 MT: H. pylori is thought to be transmitted
from person to person
- Fecal-oral transmission is likely
( It is probably acquired by ingestion)
 RF :- Use of aspirin, ibuprofen, or other
NSAID,
:- Excessive alcohol consumption,
:- Smoking cigarettes or
:- Using other tobacco products,
:- and a family history of ulcers 16

17. Epidemiology…
 RH: humans, primates, pigs
Note the following:
- Duodenal ulcerative disease usually occurs
in persons 25–75 years of age.
- Gastric ulcerative disease usually occurs in
persons 55-65 years of age.
- M/F ratio for gastric & duodenal ulcer is 2:1
- M/F ratio of acute gastritis is 1:1.
17

18. Pathogenesis
 Main virulence factors:
 Flagella: enables burrowing through stomach lining
 Adhesions: facilitates attachment to gastric cells
 Urease: neutralizes stomach acid
 Cytotoxins: contribute for gastric cell damage
 Mechanism:
- H. pylori attaches to the mucus-secreting
cells of the gastric mucosa.
- The production of large amounts of NH3
from urea by the organism's urease, coupled
with an inflammatory response, leads to damage
to the mucosa.
- Loss of the protective mucus coating
predisposes to gastric & peptic ulcer
18

19. Mechanism of H.pylori pathogenesis
19

20. Mechanism of H. pylori pathogenesis…
20
Layer of mucus
Helicobacter pylori
(neutralizes stomach
acid)
Epithelial cell
in stomach lining
Mucus-
secreting cell
Nucleus
Red blood
cells in capillaries
Bacteria invade mucus and attach to
gastric epithelial cells.
Neutrophil Lymphocyte
Helicobacter, its toxins, and
inflammation cause the layer of
mucus to become thin.
Gastric acid destroys epithelial cells
and underlying tissue.
Ulcer
Acidic gastric juice

21. Clinical manifestations
 Gastritis & PUD is characterized by:
- recurrent pain in the upper abdomen
- frequently accompanied by bleeding
in to the gastrointestinal tract.
- Sometimes vomiting blood, bloody stool
- gnawing or burning pain in the
epigastrium
 No bacteremia or disseminated
diseases occur 21

22. Laboratory Dx
 Noninvasive tests (mainly) involve:
 H. pylori serologic tests
 “Urea breath” test
Test principle
- radiolabeled urea is ingested
- If H. pylori present in the patient's stomach
- urease produced by the organism split urea
to NH3 and CO2 (radioactively labeled & exhaled)
- finally the radioactivity is detected in the breath 22

23. Diagnosis…
 H.pylori antigen test in the stool
can be used:
- for diagnosis & for confirmation
that treatment has eliminated
the organism.
 Invasive tests involve:
- Endoscopy with tissue biopsy:
 Endoscopy allows direct visualization
of gastritis, ulcers, & carcinoma
 Biopsy specimens can be tested for:
- H pylori urease activity or
- bacterial growth on culture media 23

24. Management
• Treatment:
 Antimicrobial drugs given in conjunction
with acid-blocking drugs (ABDs).
- Triple therapy with metronidazole and either
bismuth subsalicylate or bismuth subcitrate
plus either amoxicillin or tetracycline for 14
days eradicates H pylori infection in 70–95%
of patients.
- An acid-suppressing agent given for 4
to 6 weeks enhances ulcer healing.
24

25. Management…
• Prevention:
 There is no vaccine or other specific
preventive measure. But:
 Good personal hygiene, adequate sanitation
and proper food handling to decrease fecal-
oral transmission, and
 lifestyle changes to reduce risk, including:
- dietary changes to reduce stomach acid
imbalances and
- lowering consumption of alcohol, tobacco,
and aspirin-like pain medication.
25

26. D. Major pathogens of the intestine and /or liver
1. Major bacterial pathogens
1.1. Campylobacter jejuni Fig. Campylobacter demonstrating the S.shaped
(black arrow) and gull wing shaped (blue
arrow)
gram-negative rod (Gram stain).
 Disease: diarrhea (gastroenteritis)
 Medically important species:
- C.jejuni, C. coli, C. fetus
- C. upsaliensis
 C. jejuni= The most common cause
of diarrhea in human
 General property:
o Are small gram –ve rods
o Are comma, or S shaped
o Are rapidly motile by means
of a single polar flagellum
o Are microaerophilic (grow best
at reduced oxygen)
o Grow best at 5-10% CO2 & at 42 oC 26

27. Epidemiology
 RH: Campylobacter infections are
zoonotic
: Cattle, sheep, rodents, poultry,
pig, dogs, cats etc.
 MT: Infections are acquired by
consumption of contaminated
food,especially poultry, milk or water
: Person to person spread by the fecal
-oral route is rare
 RG: C. jejuni cause disease mainly in
children under 2 years
27

28. Clinical features
 Most common disease is:
- acute enteritis with diarrhea, malaise,
fever, and abdominal pain
 Most infections are self-limited but can
persist for a week or More
 C. jejuni characteristically produces histologic
damage to the mucosal surfaces of the jejunum,
ileum,and colon → Bloody diarrhea
 C. jejuni rarely cause bacteremia
- 1.5 cases per 1000 intestinal
infections
28

29. Laboratory Dx
 Stool microscopy
̶ Observation of the characteristic thin,
"S-shaped" gram –ve organisms
̶ Less sensitive but specific
 Stool antigen Detection
̶ Commercial immunoassay for detection
of C. jejuni and C. coli
̶ Has a sensitivity of 80% to 90% and
a specificity of >95%
29

30. Laboratory Dx… Fig: Campylobacter colony on CCDA
 Stool culture
̶ C. jejuni, C. coli, and C. upsaliensis
require culture at 10% CO2 & 42oC
̶ C. fetus: cannot grow at 42°C
Selective media: Charcoal Cefoperazone
Deoxycholate Modified Agar Base (CCDA)
 Biochemical test
 Oxidase and catalase positive
 Hippurate hydrolysis test:
- C. jejuni hydrolyse hipurate but
not C. coli
- +
30

31. Management
 Campylobacter gastroenteritis is typically
a self-limited infection
 Managed by the replacement of lost fluids
and electrolytes
 Antibiotic therapy may be used in patients
with severe infections or septicemia
 Proper preparation of food (particularly poultry)
 Avoidance of unpasteurized dairy products
31

32. 1.2. Vibro cholera
 Disease: Cholera
 General property:
o are comma shaped (curved),
Gm –ve bacteria
o are rapidly motile by means
of a single polar flagellum
o are facultative anaerobes
o are oxidase positive
o require NaCl & alkaline PH
for their growth
32

33. General property…
o possess both O and H antigens, but
- only O (somatic) antigens are useful
in distinguishing strains (serotypes)
of vibrios that cause epidemics
 Pathogenic vibrios include:
o V. cholerae O1 & O139 strains
- cause epidemic cholera
o Non-O1 V. cholerae & related strains
- cause sporadic cases of cholera
like & other illnesses
33

34. Etiology & general property…
o V. parahaemolyticus & other
halophilic vibrios
- cause gastroenteritis & extra
intestinal infections
 V. cholerae O1 has 2 biotypes:
- classic and El Tor
 El Tor is distinguished from
classic by:
- the production of hemolysins,
- higher carriage rates, and
- the ability to survive in water
for longer periods. 34

35. Epidemiology
 MT: Fecal –oral (contaminated water &food)
 RH: The main animal reservoirs are marine
shellfish, such as shrimp and oysters.
 N.B. Outbreaks of both O1 biotypes
have been associated with:
- raw or undercooked seafood harvested
from contaminated waters
35

36. Pathogenesis
A. Virulence factors:
o Adhesion factors
- important for colonization
o Choleragen (an enterotoxin)
- initiates an outpouring of fluid
& ions from intestine
- the organism is noninvasive,
& causes disease through the
action of cholera toxin
36

37. Clinical features
 IP: an average of 2 -3 days
 Watery diarrhea in large volumes is
the hallmark of cholera.
 No RBCs or WBCs
 Stool has a “rice-water” appearance
 It can result in the loss of one liter of
fluid every hour.
 The loss of fluid & electrolytes leads to:
- marked dehydration, cardiac/ renal failure
- acidosis & hypokalemia also occur
 mortality without treatment exceeds 50%. 37

38. Laboratory Dx
 Stool culture:
o TCBS(thiosulfate citrate bile salt)= Selective culture media
o recommended for enrichment of
stool in APW (alkaline peptone water)
 Biochemical test:
o The organism is oxidase-positive
o On TSI(triple sugar iron) agar, an acid slant & an acid
butt without gas or H2S production
 Serology & stool antigen test
o agglutination of the organism using
polyvalent O1 or non-O1 antiserum. 38

39. Management
 Antibiotics = doxycycline is the drug of choice
- It can shorten the duration of diarrhea
and excretion of the organism .
 Replacement of fluids and electrolytes is
crucial in preventing shock
 Prevention relies primarily on public health
measures that reduce fecal contamination
of water supplies and food.
 Adequate cooking of foods can minimize
transmission 39

40. 1.3. Eshericha coli
(E.coli)
General properties
• They are common normal flora of
the colon in human & animals
• They possess few exogenous strains
that cause gasteroenteritis
• They are straight gram –ve rods
• They are facultative anaerobes
• They are not fastidious bacteria
• Most strains are motile & ferment lactose
• They lack cytochrome oxidase
Epidemiology
MT: fecal-oral route
RH: both human and animals
40

41. Pathogenesis
Major virulence factors:
o Adhesins. e.g. Pili (fimbriae)
o Invasive factors. e.g.
-Invasive plasmid antigen
(by EIEC)
o Enterotoxins. e.g.
- Shiga like toxins (by EHEC)
- LT & ST (by ETEC)
N.B:- The toxins are strikingly cell-specific.
:- There are 5 major E.coli strains that cause
gastroenteritis with different pathogenesis:
- ETEC, EPEC, EHEC, EIEC, & EAEC 41

42. Pathogenesis…
Table: Gastroenteritis caused by E.coli strains
Type of
strain
Site of
action
Main Clinical disease Pathogenesis
ETEC Small
intestine
- Watery diarrhea
- It is a major Cause of
traveler’s diarrhea
Heat-stable (ST) and heat-labile (LT)
enterotoxins that stimulate hypersecretion of
fluids and electrolytes
EPEC Small
intestine
- Watery diarrhea Disruption of normal microvillus structure
resulting in malabsorption and diarrhea
EAEC Small
intestine
-Persistent watery
diarrhea
- Cause traveler’s diarrhea
Plasmid-mediated aggregative adherence of
rods (“stacked bricks”) with shortening of
microvilli, mononuclear infiltration, and
hemorrhage; decreased fluid absorption
EIEC Large
intestine
- Watery diarrhea; may
progress to dysentery with
scant bloody stools
Plasmid-mediated invasion and destruction
of epithelial cells lining colon
EHEC Large
intestine
Initial watery diarrhea
followed by grossly bloody
diarrhea (hemorrhagic
colitis); may progress to
hemolytic uremic syndrome
lesions with destruction of intestinal
microvilli, resulting in decreased absorption;
pathology mediated by cytotoxic Shiga toxins
(Stx1, Stx2), which disrupt protein synthesis
42

43. The action of ETEC LT (heat-labile toxin).[Note: ST (heat-stable
toxin)activates guanylate cyclase, causing production of cGMP
that also causes secretion.]
43

44. Laboratory Dx
 Definitive Dx of ETEC infections can be made by:
- Isolating the bacteria from stool samples on
MacConkey agar. Then
- Assaying for the toxins by ELISA or with a DNA
probe to detect the toxin genes.
 EHEC = ferment sorbitol very slowly if at all
= may be detected on MacConkey
sorbitol agar
 Other E.coli strains do ferment sorbitol
 E. coli O157:H7= does not ferment sorbitol
- which serves as an important criterion that
distinguishes it from other strains of E. coli.
 EIEC = often do not ferment lactose 44

45. Management
 Treatment of gastroenteritis caused by E coli
usually involves:
- oral replacement of the fluid & electrolytes
 Rifaximin = for the treatment of traveler’s
diarrhea caused by noninvasive strains of E coli.
 For travelers to high-risk areas, several
approaches should be encouraged to minimize
the risk of getting traveler’s diarrhea:
- instructions regarding food &beverage selection
- use of prophylactic antibiotics
 Other means of preventing these infections
include: eating foods that are freshly cooked
45

46. 1.4. Genus Shigella
-Cause shigellosis
 It is a human intestinal disease
 It is also known as enterocolitis
(bacillary dysentery)
General properties:
 The genus shigellae are:
- Facultative anaerobes
- Gram negative rods
- Non capsulated,
- Most of them All have O antigens
(polysaccharide) in their cell walls
 The “O” antigens are used to divide the
genus into four groups: A, B, C, and D.
46

47. Epidemiology
• RH: Only human. i.e; no animal reservoir
• MT: The fecal - oral route
: The 4 Fs—fingers, flies, food, and feces
are the principal factors in transmission.
• Foodborne outbreaks outnumber water-borne
outbreaks by 2 to 1.
• Children younger than 10 years of age account
for approximately half of shigella-positive stool
cultures.
• There is no prolonged carrier state with Shigella
infections, unlike that seen with Salmonella typhi
infections. 47

48. Pathogenesis
• Shigellae are the most effective pathogens
among the enteric bacteria. Why?
• They have a very low infective dose (ID50).i.e;
- Ingestion of as few as 100 organisms causes disease
- Whereas V. cholerae or S. typhi to cause disease,
ingestion of at least 105 organisms are required
• Major Virulence factors
- Shiga toxin (verotoxin) is an enterotoxin
- Type III secretion factors
- Hemolysin
N.B:- Although some strains produce shiga toxin,
invasion is the critical factor in pathogenesis.
:- Shigellae invade & destroy the mucosa of the colon.
:- Infection rarely penetrates to deeper layers
of the intestine
:- However, shigella infection does not lead
to bacteremia (often times)

49. Mechanism of Pathogenesis
A. Stages of Shigella invesion
• After adhering to the host cells, the bacteria use a type III
secretory system to inject bacterial proteins into the host cells
• These bacterial proteins cause the host cells to ruffle and ingest
the bacterial cells.
• Once in the cells, the bacteria use a surface hemolysin to lyse
the phagosome membrane and escape into the cytoplasm
• The bacteria then use the host cell’s actin to move
around inside the cell (actin rocket tails).
• When bacteria reach the periphery of the cell, the cell pushes
outward to form membrane projections, which are then
ingested by adjacent cells.
49

50. • The events of shigellosis
50
Shigella attaches to
epithelial cell of intestine
Shigella
Epithelial cell
Nucleus
Shigella triggers
endocytosis.
Shigella multiplies
in cytosol.
Actin fibers
Shigella invades
neighboring epithelial
cells, thus avoiding
immune defenses.
Mucosal abscess
An abscess forms as
epithelial cells are killed
by the infection.
Blood vessel Phagocyte
Shigella that
enters the blood
is quickly
phagocytized
and destroyed.
No bacteremia.

51. Shigella infection causing diarrhea…
51

52. Mechanism of Pathogenesis…
N.B:- The cell-to-cell travel and toxin activity
 produces superficial ulcers in the bowel mucosa &
 induces an extensive acute inflammatory response.
:- The inflammatory response usually prevents
entry of the bacteria into the bloodstream.
B. Action of shiga toxin
- which is similar to the verotoxin of EHEC O157:H7.
- The shiga toxin enters the cytoplasm of the host cells &
- Stops protein synthesis by removing an adenine residue
from the 28S rRNA in the 60S ribosomal unit.
- This toxic activity results in death of the host cells. 52

53. Clinical manifestations
 Shigellae cause classic bacillary dysentery;
 Shigellosis is characterized by diarrhea with
blood, mucus, and painful abdominal cramping
 Group A and B shigella species usually
cause dysentery
 Group C and D usually cause watery diarrhea
• Among uncompromised populations,
- untreated dysentery commonly resolves
in a week, but maypersist longer. 53

54. Diagnosis
• Presumptive diagnosis of shigellosis is based on:
- acute onset of fever and diarrhea with bloody
and mucoid feces.
• Definitive diagnosis requires the isolation of
Shigellae from feces:
- Shigellae form NLF colonies on MacConkey's agar.
- On TSI agar, they cause an alkaline slant & an acid
butt, with no gas and no H2S production.
 Abscesses in a rectal biopsy are suggestive of shigellosis.
 Confirmation of the organism as Shigella & determination
of its group are done by slide agglutination.
54

55. Management
 The main treatment for shigellosis is fluid
and electrolyte replacement.
 In mild cases, no antibiotics are indicated.
 In severe cases, a fluoroquinolone
(e.g., ciprofloxacin) is the drug of choice
 Prevention of shigellosis is dependent on
interruption of fecal–oral transmission by:
- proper sewage disposal, chlorination of water, and
personal hygiene (hand washing by food handlers).
 There is no vaccine, and
55

56. 1.5. Genus Salmonella
- Cause samonelosis
General property
 Salmonellae are:
- Gm –ve rods, NLFs, facultative anaerobes,
- Produce H2S, Usually motile
- produce gas from glucose fermentation
 Clinically, salmonella species are divided
in two distinct categories:
- The TS (S.typhi, S.paratyphi)=cause enteric fever
- The NTS (S.thyphimurum, S.enteritidis etc=
cause diarrhea, and Metastatic infection
56

57. Epidemiology
 RH :- only humans for typhoidal salmonellosis (TS)
:- animal as well as human reservoir for (NTS).
 SI :- poultry products: raw/lightly cooked eggs (NTS)
:- potatoes, raw milk, raw meat, pet animals (NTS)
:- human healthy carriers only (TS)
 MT :- fecal – oral route (for both cases)
:- contaminated foods or drinks (both)
:- handling of animals (NTS)
Pathogenesis
- Almost similar to shigellosis
-- But here bacteremia occurs 57

58. 58
Epithelial
cell
Nucleus
Salmonella
Salmonella attaches to
epithelial cells lining
the small intestine.
Salmonella triggers
endocytosis.
Salmonella multiplies
within food vesicle.
Salmonella kills host
cell, inducing fever,
cramps, and diarrhea.
Capillary (blood vessel)
Bacteremia:
Salmonella
moves into
bloodstream.

59. Clinical manifestations
 For gastroenteritis:
- Nausea, vomiting, diarrhea,
- Abdominal discomfort
 For enteric fever:
- Acute febrile illness
- Hepatosplenomegally
- Gall bladder infection
- Re-infection of intestinal tract:
intestinal perforation 59

60. Diagnosis
 In patients with diarrhea:
- Salmonella can typically be isolated from
stools: on MacConkey agar or
: 0n selective media
 In patients with enteric fever:
 appropriate specimens include:
blood, bone marrow, urine, stool, & tissue
 when the organism is difficult to recover, the
diagnosis can be made serologically by:
- detecting a rise in antibody titer in the
patient's serum (Widal test) 60

61. Management
Treatment
 For gastroenteritis:
- In uncompromised hosts, antibiotic therapy
is often not needed
 For enteric fever:
- appropriate antibiotics include β-lactams
and fluoroquinolones .
Prevention
- proper sewage disposal, correct handling
of food, and good personal hygiene.
- Vaccine available for preventing S.typhi
61

62. Comparison of salmonella and Shigella
Feature Shigella Salmonella (NTS) Salmonella (TS)
Reservoir Humans Animals, especially
poultry and eggs
Humans
Infectious dose Low High High
Diarrhea as a prominent feature Yes Yes No
Invasion of blood stream No Yes Yes
Chronic carrier state No Infrequent Yes
Lactose fermentation No No No
H2S production No Yes Yes
Vaccine available No No Yes
62

63. 1.6. Clostridium difficil
- Cause pseudomembraneus
colitis
 General properties
• Gram +ve spore-forming rods
• Are obligate anaerobes
• It is a normal intestinal flora
• Inhabits in the human colon
 Epidemiology
• MT: fecal–oral, endogeneous
 Pathogenesis
A. virulence factors
- Has two toxins: Toxin A (enterotoxin),
Toxin B (extremely lethal/
cytopathic toxin)
•
63

64. Pathogenesis…
B. How it causes colitis?
 Antibiotics suppress normal flora of colon
 Allowing C. difficile to overgrow & produce
• large amounts of exotoxins
• Exotoxins A and B inhibit GTPases, causing:
- inhibition of signal transduction and
- depolymerization of actin filaments
 This leads to apoptosis & death of enterocytes.
- The pseudomembranes seen in the colon are
the visual result of the death of enterocytes.
64

65. Clinical diseses
• mild to moderate form of diarrhea, termed
antibiotic-associated diarrhea
• Plaques and microabscesses may be localized
to one area of the bowel.
• The diarrhea may be watery or bloody, and
• the patient frequently has associated abdominal
cramps, leukocytosis, and fever
Diagnosis
• detection of one or both C difficile toxins in stool
• endoscopic observation of pseudomembranes
or microabscesses in patients who have diarrhea
• Treatment: Metronidazole is the drug of choice
• Prevention: No vaccine 65

66. 2. Major Viral Pathogens
2.1. Rota virus
 General property
 Rota viruses:
o belong to the family reoviridae
o are non enveloped viruses
o possesses ds RNA genome
o possesses double layered
icosahedral capsid
o contain an RNA dependent
RNA polymerase.
o replicate in the cytoplasm
o are divided into 7 serogroups (A to G)
o Only A, B, & C serogroups infect human 66

67. General property…
 Group A are the major cause of
outbreaks of disease in human
 Rota virus are the most common
cause of viral gastroenteritis in
young children & infants
 Other causes of viral gastroenteritis:
o Norwalk/Norovirus
- belong to the family caliciviridae
- affects primarily adults and old
children, but not infants
o Astrovirus= bélong to astroviridae
o Adénovirus=bélong to adenoviridae 67

68. Epidemiology
 MT : fecal–oral route (e.g. contaminated
water or food
 GD : Worldwide (but higher prevalence
in developing countries
 RH : Human and Animals
 N.B: Rotavirus infections are more
common in the winter
: In adults, the disease tends
to be mild. 68

69. Mechanism of rotavirus diarrhea
- the diarrhea is non bloody
69

70. Clinical features
 IP: is usually 48 hours or less.
 Infection can be subclinical or
may result in symptoms
 Symptoms ranging from:
o mild diarrhea and vomiting
o to severe watery diarrhea with
dehydration & loss of electrolytes
 Gastroenteritis is most serious in
young children
 Adults usually have minor symptoms 70

71. Diagnosis
 Definitive diagnosis cannot be made
on clinical grounds alone
 So, identification can be made by
using:
o Serological test: ELISA or RIA test
o Electron microscopy of stool specimens
o Viral culture: not routinely done
71

72. Management
 Treatment
o No specific antiviral drug appropriate
for treatment of rotavirus infection
o Most important clinical intervention
is rapid & efficient replacement of
fluids and electrolytes
 Prevention
o Oral vaccines
o Improved sanitation measures 72

73. 2.2. Hepatitis virus
 Many viruses cause hepatitis
 Of these, 5 medically important viruses are
commonly described as "hepatitis viruses“
- b/c their main site of infection is the liver
 These are: HAV,HBV,HCV,HDV,& HEV
 Other viruses, such as EBV, CMV, & yellow
fever virus, infect the liver but also infect
other sites in the body
- therefore are not exclusively
hepatitis viruses. 73

74. 2.2.1. Hepatitis A virus (HAV)
 HAV cause hepatitis A
General property
• HAV is also known as enterovirus 72
• It is a typical enterovirus classified in
the picornavirus family
• It has ss (+)RNA genome
• It is a non enveloped virus
• It has icosahedral nucleocapsid
• It replicates in the cytoplasm of the cell
• It is quite stable in the environment 74

75. Epidemiology
 MT: fecal-oral route is the primary means of HAV
transmission:
- Outbreaks of HAV infection occur following
ingestion of raw shellfish harvested from
fecally contaminated water.
: HAV infection is rarely transmitted via blood
- b/c it has transient & low level viremia
 RH: Humans and lower primates
 RG: Children are the most frequently
infected groups 75
rarely transmitted

76. Epidemiology…
• About 44% of cases of viral hepatitis are
caused by HAV, 49% by HBV, & 7% by HCV.
• The incidence of HAV infection is higher in
areas of low socioeconomic development.
- >90% of the population in developing
countries has been infected with HAV
- <50% of the population in developed
countries has been infected with HAV
• MRs: are very low in cases of HAV infection
(0.1–0.2%)
• A chronic carrier state does not occur in
patients infected with HAV. 76

77. Pathogenesis
 The pathogenesis of HAV infection is not
completely understood.
 The virus probably replicates in the GIT
and spreads to the liver via the blood.
 Hepatocytes are infected, but the mechanism
by which cell damage occurs is unclear.
- HAV infection of cultured cells produces no CPE
- It is likely that attack by cytotoxic T cells causes
the damage to the hepatocytes.
 The infection is cleared, the damage is repaired,
and no chronic infection ensues.
77

78. Clinical manifestations
 Initial symptoms of HAV include:
- Fever, anorexia, nausea, vomiting,
- Hepatosplenomegaly
 Classic symptoms that develops later include:
- cholestasis, jaundice & elevated transaminase
levels (AST, ALT, and bilirubin)
 Most cases resolve spontaneously in 2 to 4 weeks
 Hepatitis A has a short incubation period (3–4 weeks)
 Most HAV infections are asymptomatic
 There is no predisposition to hepatocellular carcinoma 78

79. Diagnosis
• Diagnosis of viral hepatitis includes:
- Identifying clinical signs and symptoms
- Blood studies reveal elevated liver enzyme
levels (ALT and AST).
- Serologic testing aids in confirmation of
the clinical diagnosis
E.g. The detection of IgM antibody is the most
important test 79

80. Treatment and Prevention
 No antiviral therapy is available
- Supportive care and rest are currently
the only treatment for patients with
viral hepatitis
 Prevention depends on:
- taking measures to avoid fecal
contamination of food &water
 HAV vaccine is available 80

81. 2.2.2. Hepatitis B virus (HBV)
 HBV causes hepatitis B
General property
 HBV is a member of hepadnavirus family
 It is enveloped with icosahedral neucleocapsid
 It has a partially ds circular DNA genome
 The genome contains 4 genes that encode
five proteins:
1. S-gene = encodes surface antigen (HBsAg)
2. C-gene = encodes the core antigen (HBcAg) &
= encodes the e antigen (HBeAg)
3. P-gene = encodes DNA polymerase 81

82. Hepatitis B virus (HBV)…
4. X-gene = encodes x-protein
Note: X-protein = is an activator of viral RNA transcription
: DNA polymerase = has both RNA dependent and
DNA dependent activity
: HBsAg = is an envelope protein
= is important for laboratory
Dx and immunization
: HBcAg = is a core protein
= forms the nucleocapsid core for the virion
: HBeAg = is secreted from infected cells in to the blood
= is an important indicator of transmissibility
82

83. Epidemiology
 MT: The 3 main modes of transmission are:
- Via blood
- During sexual intercourse, and
- Perinatally from mother to newborn
 RH : Humans and chimpanzee are the
only reservoir hosts
 GD: HBV is a world wide infection
 SI : HBV is present in all body fluids of an
infected individual
: therefore, blood, semen, saliva, and
mother's milk, for example, serve as
sources of infection. 83

84. Epidemiology…
N.B. The titer of infectious virus in the blood of an
acutely infected patient can be as high as 108
virus particles per ml, but generally is lower in
other body fluids.
 RG: Persons at high risk for HBV Infection:
● Intravenous drug users
● Patients undergoing blood transfusions or hemodialysis
● Personnel in contact with blood and blood products
● Persons with multiple sexual contacts (heterosexual
and homosexual)
● Immunosuppressed persons
● Infants born to mothers with chronic HBV 84

85. Pathogenesis
• After entering the blood, the virus infects hepatocytes,
and viral antigens are displayed on the surface of the cells.
• Cytotoxic T cells mediate an immune attack against the viral
antigens, and inflammation and necrosis occur. Because HBV
itself does not cause a cytopathic effect.
 About 5% of patients with HBV infection become chronic carriers
 Approximately 90% of infected neonates become chronic carriers.
 Chronic carriage resulting from neonatal infection is associated with
a high risk of hepatocellular carcinoma
85

86. Clinical manifestations
 IP: the mean IP for Hepatitis B is 10-12 weeks
 HBV cause acute and chronic (cirrhosis & liver
cancer or HCC) disease
 The clinical appearance of acute hepatitis B is similar
to that of hepatitis A.
 However, with hepatitis B, symptoms tend to be more
severe, and life-threatening hepatitis can occur
 Most chronic carriers are asymptomatic, but some have
chronic active hepatitis, which can lead to cirrhosis and death 86

87. Clinical outcomes of acute HBV infection
87

88. Diagnosis
 The diagnosis of hepatitis is made on clinical grounds,
coupled with biochemical tests.
 Elevations of aminotransferases, ALP, and bilirubin all
contribute to the initial evaluation of hepatitis.
 ELISA and other immunologic techniques for detection of
viral antigens and antibodies:
- Helps for the primary means to distinguish among
Hepatitis viruses.
- Permits differentiating between acute and chronic
HBV infections 88

89. Serologic test result in 4 stages of HBV infection
Test Acute
Disease
Window
phase
Complete
recovery
Chronic carrier state
HBeAg Positive Negative Negative Positive/-
HBsAg Positive Negative Negative Positive
HBeAb Negative Negative Positive Negative
HBsAb Negative Negative Positive Negative
HBcAb Positive Positive Positive Positive
89

90. Treatment and Prevention
• Treatment of acute infections with HBV involves supportive care.
• Treatment of chronic HBV infections can include human
interferon alpha (IFN), lamivudine (3TC),or adefovir dipivoxil
• Adefovir dipivoxil and lamivudine are nucleoside-nucleotide
analogues that suppress HBV replication through inhibition
of HBV-DNA polymerase.
 Treatment with conventional IFN results in loss of
viremia and normalization of liver enzymes
 Prevention involves the use of either the vaccine or
hyperimmune globulin or both. 90

91. 2.2.3. Hepatitis C virus (HCV)
 HCV causes hepatitis C.
 HCV is a member of the flavivirus family
 It is an enveloped virus
 It has ss (+) RNA genome
 It has no virion polymerase
 Humans are the reservoir for HCV
 The MT is similar to HBV transmission
 The disease is world wide in distribution
 It is associated with both acute & chronic hepatitis
 HCV infects hepatocytes primarily, but there is no evidence
for a virus-induced cytopathic effect on the liver cells
 Almost its pathogenesis is similar to HBV.
91

92. Hepatitis C virus (HCV)…
 Clinically, the acute infection with HCV is milder than infection with HBV
 Hepatitis C resembles hepatitis B as far as the ensuing
chronic liver disease, cirrhosis, and the predisposition to
hepatocellular carcinoma are concerned
 Diagnosis of HCV infection= same as HBV
 Treatment of acute infections with HBV involves supportive care.
 Two different treatment strategies exist for treating chronic
HCV patients:
(1) immediate treatment with Peginterferon alfa-2a and ribavirin
for up to 48 weeks; or
(2) liver biopsy performed every 3 years and drug therapy
 There is no vaccine, and hyperimmune globulins are not available
92

93. 2.2.4. HDV or Delta virus
 HDV causes hepatitis D (hepatitis delta).
 HDV is an enveloped virus
 It has ss (-) RNA genome
 It has no virion polymerase
 HDV cannot replicate by itself because it does
not have the genes for its envelope protein.
- So, it can replicate only in cells also infected with HBV
because HDV uses the surface antigen of HBV (HBsAg)
as its envelope protein.
- HBV is therefore the helper virus for HDV
 The pathogenesis is the same as HBV
 MT: Similar to HBV, GD: world wide, RH: Human only 93

94. HDV or Delta virus…
 Clinical disease:
- Cause both acute & chronic disease
- Hepatitis in patients co-infected with HDV
and HBV is more severe than in those infected
with HBV alone,
- but the incidence of chronic hepatitis is about
the same in patients infected with HBV alone.
 Diagnosis: the same as HBV
 There is no specific antiviral therapy against HDV.
 There is no vaccine against HDV, but a person immunized
against HBV will not be infected by HDV.
- B/c HDV cannot replicate unless HBV infection also occurs.
94

95. 2.2.5. Hepatitis E virus (HEV)
• HEV is a common cause of water borne epidemics of hepatitis
• HEV is a major cause of enterically transmitted hepatitis.
• It is classified as a member of the calicivirus family
• It is a non enveloped virus
• It is ss (+) RNA virus
• Clinically the disease resembles hepatitis A
- With the exception of a high mortality rate in
pregnant women.
- Chronic liver disease does not occur, and there is
no prolonged carrier state.
• The test for HEV antibody is not readily available
• There is no antiviral treatment and no vaccine 95

96. 2.2.6. Hepatitis G virus (HGV)
 HGV is a member of the flavivirus family
 HGV Not cause hepatocellular carcinoma
 Non pathogenic form of the virus
 MT:- via sexual intercourse & parenteral
 Patients co-infected with HIV and HGV:
- have a lower mortality rate and
- have less HIV in their blood than
those infected with HIV alone.
• b/c It is hypothesized that HGV may
interfere with the replication of HIV
96

97. Summary
Comparison of Hepatitis virus
97

98. 98

99. Reading assignment
 GIS infection due to Bacterial
food poisoning
99

100. References
 Jawetz M et al; Medical microbiology, 26th edition (2013)
 Murray R et al; Medical microbiology, 6th edition (2010)
 Mims et al; Medical microbiology, 3rd edition (2003)
 James J.Champoux et al; Sherris Medical
microbiology, 4th edition (2004)
 Connie R. Mahon et al; Text book of diagnostic
microbiology, 4th edition (2011) 100