Neely: Intra-Abdominal Infections I Flashcards
1
Q
NORMAL FLORA OF INTESTINAL TRACT
Mouth:
Stomach:
A
Mouth: thousands of bacteria in the mouth; many more anaerobes (100:1); main reservoir for introduction into intestinal tract
Stomach: acidic environment where most oral bacteria killed; similar bacteria to those in mouth and throat.
2
Q
NORMAL FLORA OF INTESTINAL TRACT
Stomach to Small Intestine:
What type of bacteria?
Colon:
What type of bacteria?
A
Stomach to Small Intestine: mostly Gram positive
- Enterococcus: can live in the presence of bile salts (highest concentration in duodenum).
Colon: beneficial bacteria; mostly anaerobes (1000:1)
- 400-500 different species (mainly strict anaerobes; therefore cannot be cultured)
- Do not cause disease in the environment (only if they get into normally sterile parts of the body)
3
Q
PROTECTION OF THE INTESTINAL TRACT
Mucous Membranes
Goblet Cells Produce?
Lubricant does what?
Physical barrier:
A
Goblet Cells: produce mucus
Lubricant to protect mucous membrane
Physical barrier to trap bacteria that is expelled by peristalsis
4
Q
PROTECTION OF THE INTESTINAL TRACT
Mucous Membranes
M Cells Aid in:
What do M cells phagocytose?
A
M Cells: aid in presentation of antigens to underlying cells of the immune system (in Peyer’s patches)
Phagocytose bacteria and other Ags and pass to macrophages under the M cell
5
Q
PROTECTION OF THE INTESTINAL TRACT
Mucous Membranes
Absorptive Cells (Enterocytes): What do Bacteria that reach mucosal cells have to deal with? Mucosal cells formed in? Move up what? Are released into:
A
Absorptive Cells (Enterocytes): some of the most rapidly dividing cells in the body
Bacteria that reach mucosal cells have to deal with rapid turnover
Mucosal cells formed in crypts, move up the villous surface, and are released into the lumen as new cells replace them
6
Q
PROTECTION OF THE INTESTINAL TRACT
Other Protective Mechanisms: (5)
A
- sIgA
- Stomach acid
- Bile salts
- Rapid flow of material through small intestine (washes bacteria out of SI)
- Slow rate of material through colon with dense bacterial population (protective normal flora)
7
Q
PROTECTION OF THE INTESTINAL TRACT
When does infection occur?
A
Infection occurs when organisms with virulence mechanisms overcome the protective mechanism of the GI tract
8
Q
What tests identify gram negative bacteria?
A
Oxidase Reaction
Growth on MacConkey agar
Metabolism - Oxidative or fermentative
9
Q
What does the oxidase reaction detect?
What is Mac agar selective for?
3 types of metabolism:
A
Oxidase Reaction: detects presence of cytochrome oxidase (transfers electrons to O2)
Growth on MacConkey agar: selective for Gram negative
Metabolism: oxidative, fermentive or inert
10
Q
Enterobacteriaceae
Oxidase:
MacConkey Growth/Color:
Metabolism:
A
Oxidase: Negative
MacConkey Growth/Color: Yes/Varies by species
Metabolism: Fermentation
11
Q
Vibrionacea
Oxidase:
MacConkey Growth/Color:
Metabolism:
A
Oxidase: Positive
MacConkey Growth/Color: Yes/Colorless to light pink
Metabolism: Fermentation
12
Q
Campylobacteriaceae
Oxidase:
MacConkey Growth/Color:
Metabolism:
A
Oxidase: Positive
MacConkey Growth/Color: No growth
Metabolism: Inert
13
Q
Pseudomonadaceae
Oxidase:
MacConkey Growth/Color:
Metabolism:
A
Oxidase: Positive
MacConkey Growth/Color: Yes/Colorless
Metabolism: Oxidative
14
Q
Enterobacteriaceae family includes: (6)
A
Enterobacteriaceae family includes
E.coli Klebsiella Salmonella Shigella Yersinia Proteus
(YEP KiSS)
15
Q
Enterobacteriaceae
G+/-:
Shape:
Aerobe or anaerobe?
A
All are Gram negative rods and facultative anaerobes
16
Q
Is Campylobacteriaceae G+ or -?
A
G-, but does not grow on MacConkey; Requires a specialized media to grow.
17
Q
BACTERIAL AND PARASITIC GI INFECTIONS:
Terms
Secretory:
Non-inflammatory:
Inflammatory:
*Invasive:
A
Secretory: watery, non-inflammatory
Non-inflammatory: no leukocytes in the stool
Inflammatory: presence of leukocytes in the stool
Invasive: organism can invade into the epithelial cells
18
Q
BACTERIAL AND PARASITIC GI INFECTIONS:
Terms
*Non-Invasive:
Enterotoxin:
Neurotoxin:
Cytotoxin:
A
Non-Invasive: bacteria stay in the lumen, but may cause disease by secreting toxins
Enterotoxin: toxin released by a microorganism in the intestine
Neurotoxin: toxin that acts directly on neurons
Cytotoxin: toxin having a specific toxic action on cells of special organs
19
Q
Secretory Diarrhea (Non-Invasive and Non-Inflammatory) caused by:
A
Secretory Diarrhea (Non-Invasive and Non-Inflammatory): caused by toxogenic bacteria, noninvasive parasites, or virus
20
Q
Secretory Diarrhea (Non-Invasive and Non-Inflammatory)
Bacterial Enterotoxigenic Diarrhea: (2)
A
Enterobacteriaceae and Vibrionaceae
21
Q
Secretory Diarrhea (Non-Invasive and Non-Inflammatory)
Bacterial Neurotoxin Group: (3)
A
Bacterial Neurotoxin Group: ingested organisms produce a neurotoxin (usually the preformed toxin is ingested)
C.botulinum, B.cereus, S.aureus
22
Q
Secretory Diarrhea (Non-Invasive and Non-Inflammatory)
Non-Inflammatory Parasitic: (2)
A
Non-Inflammatory Parasitic: G.lamblia, C.parvum
23
Q
Invasive/Tissue Damaging Diarrhea (Inflammatory)
Bacterial Cytotoxin Caused Inflammation: (2)
A
C.difficile, EHEC
24
Q
Invasive/Tissue Damaging Diarrhea (Inflammatory)
Bacterial Invasive Infection: (3)
A
Shigella, Salmonella, EIEC
25
Invasive/Tissue Damaging Diarrhea (Inflammatory)
Parasitic Invasive: (1)
E.histolytica
26
Miscellaneous Intestinal Infections:
Gastric and duodenal ulcers:
Food-borne bacteremia and meningoencephalitis:
Parasitic GI Helminths
Gastric and duodenal ulcers: H.pylori
Food-borne bacteremia and meningoencephalitis: L.monocytogenes
Parasitic GI Helminths
27
Vibrio Cholerae (O1 and O139)
G+/-?
Ox +/-?
Shape:
Grows in:
Vibrio Cholerae (O1 and O139)
Gram negative
Oxidase positive
Comma shaped motile rod
Grows in freshwater ponds and brackish water (can colonize shellfish)
28
```
Vibrio Cholerae (O1 and O139)
Virulence Factors
```
Motility
Adherence
Cholera Toxin (Choleagen)
29
```
Vibrio Cholerae (O1 and O139)
Motility via:
```
Motility: single polar flagellum
30
What is Cholera Toxin aka?
A subunit:
B subunit:
Cholera Toxin (Choleagen): A-B type ADP-ribosylating toxin
A subunit: enzymatic; only 1 subunit
B subunit: binding; 5 identical subunits
31
Vibrio Cholerae (O1 and O139)
Adherence via: (2)
What does this allow the bacteria to do?
What is Tcp pili?
Adherence: pili and other adhesins (most important VF)
Allow bacteria to adhere tightly to the epithelium of the SI
Tcp pili= toxin co-regulated pili (long, filamentous pili)
32
Vibrio Cholerae (O1 and O139)
What does the toxin attach to?
What does it bind?
Toxin attaches to the surface of a mucosal cell (binds GM1 gangliosides)
33
Vibrio Cholerae (O1 and O139)
What is released from the toxin? What does it enter?
What does A1 subunit do to Gs?
A1 subunit is released from the toxin (choleagen) and enters the host cell
A1 subunit ADP-ribosylates membrane protein Gs (turns on adenylate cyclase constitutively)
34
Vibrio Cholerae (O1 and O139)
What causes an increase in cAMP?
Increase in cAMP causes ion imbalance that results in: (3)
Adenylate cyclase causes an increase in cAMP
Increase in cAMP causes ion imbalance that results in:
Water loss (the major effect of cholera)
Hypersecretion of fluids and chloride ions
Inhibition of sodium absorption.
35
Vibrio Cholerae (O1 and O139)
Onset time:
Sensitivity to stomach acid:
Replication:
Rapid onset 2-3 days after inoculation
Need to ingest a lot because of sensitivity to gastric acids (~108 cfu)
Replicates to very high numbers
36
Vibrio Cholerae (O1 and O139)
Attaches to:
Produces and secretes:
Attachment to epithelial cells in the small intestine (flagella and pili help).
Produces and secretes CTX toxin.
37
Vibrio Cholerae (O1 and O139)
Initial Clinical Manifestations: (3)
Net result:
Initial Clinical Manifestations:
- Vomiting
- Massive watery diarrhea with mucous flecks (rice-water stools)
- No PMNs in stool
Rapid dehydration and electrolyte loss
38
Vibrio Cholerae (O1 and O139)
Transmission:
Carriers:
Fecal-Oral: via water, fish, and shellfish
Carriers: recovered patients can still shed the organism (important in endemic regions)
39
Vibrio Cholerae (O1 and O139)
Clinical Identification:
Lab Tests:
Ox +/-?
Special Medium:
Clinical Identification: Stool specimen only
Lab Tests: oxidase positive, curved Gram negative rod
Special Medium: thiosulfate citrate bile sucrose (TCBS)
40
Vibrio Cholerae (O1 and O139)
Two biotypes of O1 V. cholerae:
Antigens: O1 and O139 are markers for strains that produce cholera toxin (the others do not, and therefore only produce non-epidemic diarrhea and extra-intestinal infections)
Epidemic Cholera via O1 and O139:
- Classic: More virulent
- El Tor (worse): Survives better
41
GDP + Gs =
GTP + Gs =
Gs + CTX =
GDP + Gs = no activation
GTP + Gs = transient activation
Gs + CTX = continuously activates Adenylate cyclase
42
What is the most common cause of traveler's diarrhea?
| Where is the highest incidence?
Enterotoxigenic E.Coli (ETEC): Most common cause of Traveler’s diarrhea
Highest incidence in the tropics and in the young
Similar to Vibrio cholera.
43
Types of pathogenic E.coli (5):
Enterotoxogenic (ETEC)
Enteroadherent (EAEC) or Enteroaggregative (EAggEC)
Enteropathogenic (EPEC)
Enteroinvasive (EIEC)
Enterohemmorrhagic (EHEC)
44
Enterotoxigenic E.Coli (ETEC)
| Virulence Factors: (2)
Adherence
| Endotoxins
45
Enterotoxigenic E.Coli (ETEC)
Adherence:
Where are adhesins? What do they bind?
What is the bundle-forming pilus similar to?
Adherence:
Adhesins: colonization factors on pili (bind epithelial cells in SI)
Bundle-forming pilus: similar to Tcp pili in V.cholerae
46
Enterotoxigenic E.Coli (ETEC)
| Exotoxins (2):
Heat Labile Toxin (LT)
| Heat Stable Toxin (ST)
47
Enterotoxigenic E.Coli (ETEC)
Heat Labile Toxin (LT)
Inactivated at what temp?
How similar is it to cholera toxin?
Binds what receptor?
Secreted by what mechanism?
Heat Labile Toxin (LT): inactivated at 100 degrees C for 30 minutes
Shares ~75% aa sequence with cholera toxin
5B:1A subunit (same structure as cholera toxin)
Binds same receptor (GM1 ganglioside) and has the same MOA as cholera toxin
Heat stable ST toxin is secreted by type II secretion
48
Enterotoxigenic E.Coli (ETEC)
Heat Stable Toxin (ST)
What happens at 100 degrees C?
Family of small molecules or a single toxin?
MOA:
Result:
Heat Stable Toxin (ST): not inactivated at 100 degrees C for 30 minutes
Family of small molecules (not a single toxin)
MOA: binds a guanylate cyclase in the membrane of the host cell, resulting in activate and increase in cGMP
Result: fluid and electrolyte loss
49
Enterotoxigenic E.Coli (ETEC)
Colonizes:
What leads to diarrhea?
Etiology/Pathogenesis:
Colonizes the SI with adhesins
Production of LT and ST leads to diarrhea
50
Enterotoxigenic E.Coli (ETEC)
Incubation period:
Starts as:
Progresses to:
Clinical Manifestations: incubation period of 1-2 days
Starts as: nausea, vomiting, weakness, dizziness and abdominal pain; also a low grade fever
Progresses to: watery diarrhea (mild to severe)
51
Enterotoxigenic E.Coli (ETEC)
Transmission:
Contaminated food and beverages are the major vehicles of transmission
52
Enterotoxigenic E.Coli (ETEC)
Identification of Organism:
ELISA or agglutination tests for presence of toxins
DNA probes for LT or ST genes
53
Enteropathogenic E.Coli (EPEC)
Causes:
Previously associated with:
Can cause:
o Causes severe (often fatal) watery diarrhea in infants and children in developing countries
o Previously associated with outbreaks in nurseries in developed countries
o Can cause Traveler’s diarrhea in adults
54
Enteropathogenic E.Coli (EPEC)
Virulence Factors
Attaching and Effacing Lesion
```
Non-intimate binding:
- occurs via:
Intimate binding:
- mediated by:
Effacement of the cell membrane:
```
Non-intimate binding: occurs via the bundle-forming pilus
Intimate binding: mediated by bacterial proteins (Tir and intimin)
Effacement of the cell membrane: loss of microvilli and the formation of a pedestal-like structure beneath the organism
55
Enteropathogenic E.Coli (EPEC)
Virulence Factors
What type of secretion?
Type III Secretion: proteins injected right into the cell so that Abs to the proteins never see them
Injects a receptor for itself into the cell (allows it to bind any cell)
56
Enteropathogenic E.Coli (EPEC)
Etiology/Pathogenesis:
What can cause death?
What is malabsorptive diarrhea caused by?
Dehydration and electrolyte balance can cause death
Malabsorptive Diarrhea: most likely caused by a loss of absorptive capacity of mucosal cells due to damage of the host cell surface
57
Enteropathogenic E.Coli (EPEC)
| Symptoms: (3)
Watery diarrhea (non-bloody, mucous-filled)
Fever
N/V
58
Enteropathogenic E.Coli (EPEC)
Transmission:
Identification:
Transmission: Fecal-oral route
Identification: ELISA and multiplex PCR
59
Clostridium botulinum
Botulinal Toxin
What type of toxin?
What is death usually due to?
What type of toxin? what does it bind?
Botulinal Toxin: neurotoxin; usually ingested as a preformed toxin and travels in the bloodstream to neurons, resulting in flaccid paralysis (death usually due to respiratory collapse)
AB Toxin: B portion binds ganglioside receptors on nerve cells.
60
Clostridium botulinum
What does Botulinal Toxin block?
How can you inactivate it?
Toxin internalized and blocks presynaptic release of ACh at the NMJ (prevents muscle contraction).
Can be inactivated by boiling for 10-15 minutes.
61
Clostridium botulinum
Spores
Heat resistance:
Locations:
Spores are heat resistant: can withstand 100 degrees Celsius for 3-5 hours
Spore Locations: found in animal feces, soil and lake sediment
62
Types of Botulism: (3)
Food Botulism
Infant Botulism
Wound Botulism
63
Food Botulism
What is the result?
How long does it take for side effects to occur?
Spore germinates in foods, resulting in bacterial growth and toxin production (food needs to be anaerobic, like canned goods)
Ingestion of preformed toxin, which is absorbed in the stomach and enters the bloodstream; Sx occur 12-36 hours later
64
Infant Botulism
What can happen to the infant's colon?
Rare cause of:
C.botulinum can colonize the infant colon (ie. spores in honey), and since they are without complete colonic microflora, it can grow and produce toxin
Rare cause of Sudden Infant Death Syndrome
65
Wound Botulism:
Spores colonize deep wounds (anaerobic), grow and produce toxin that enters the bloodstream
66
Clostridium botulinum
Associated with diarrhea?
Recovery period:
Not associated with diarrhea
Recovery period is long: affected nerve endings need to regenerate
67
Clostridium botulinum
Identification of Organism:
Anaerobic?
G +/-?
Lab confirmation by:
Anaerobic, Gram negative, spore-forming bacillus
Organism can be grown in oxygen free lab environment
Laboratory confirmation by immunoassay for toxin in food, gastric contents or blood
68
What is the most common bacterial form of food poisoning?
Staphylococcus aureus
69
Staphylococcus aureus
| Virulence Factors:
Pre-formed toxin (enterotoxin)
70
Staphylococcus aureus
Pre-formed toxin (enterotoxin)
Pre-formed toxin (enterotoxin): ingested and absorbed into the gut, stimulating neural receptors
- Stimulus transferred to the vomiting center in the CNS
71
Staphylococcus aureus
Symptoms (2):
Symptoms:
o Vomitting (projectile) within hours
o Diarrhea less frequently
72
Staphylococcus aureus
Transmission:
Transmission:
o Can multiply/make toxins in foods that are unrefrigerated for extended periods of time
o Re-heating the food does not destroy the heat-stable enterotoxins
73
Bacillus cereus
2 Forms:
Emetic (Vomiting) Form
| Diarrheal Form
74
Bacillus cereus
Emetic (Vomiting) Form
```
Cause:
Associated with:
Incubation period:
Symptoms:
Duration:
```
Cause: ingestion of pre-formed heat stable enterotoxin ingested in reheated foods
Often associated with Chinese restaurants (fried rice)
Short incubation period: 1-6 hours (rapid onset)
Symptoms: N/V and abdominal cramps (similar to S.aureus food poisoning)
Duration: usually 24 hours or less
75
Bacillus cereus
Diarrheal Form
```
Cause:
Associated with:
Incubation period:
Symptoms:
Duration:
```
Cause: heat-labile toxin formed in vivo, which activates adenylate cyclase and causes intestinal fluid secretion
Associated with meat or vegetable containing foods after cooking (food held above room temperature for a prolonged period)
Long incubation period: 8-16 hours
Symptoms: severe abdominal cramps and diarrhea (may be a small volume or profuse and watery)
Duration: usually 24 hours or less
76
C.perfringens
Similar to:
Cause:
- Where is C.perfringens type A produced?
Very similar to B.cereus diarrheal form
Cause:
o Temperature abuse of prepared foods (meat, meat products, gravy)
o Contaminated with enterotoxin producing C.perfrigens type A (toxin produced in GI tract)
77
C.perfringens
Onset:
Symptoms:
Onset: 8-24 hours after ingestion of contaminated meat
Symptoms: abdominal cramps and watery diarrhea
o Without fever, nausea or vomiting
78
Giardia lamblia
Basics:
Virulence Factors
Life Cycle:
Adhesion:
Flagella:
Basics: flagellated, enteric protozoan
Virulence Factors:
Life Cycle: two stages- trophozoite (free living) and cyst (infective)
Adhesion: via sucking/adhesive disk on the trophozoite; adheres to upper SI mucosal surface
Flagella: motility and attachment
79
Giardia lamblia
*Etiology/Pathogenesis*
Infection due to:
Associated with:
Incubation:
Infection: due to oral ingestion of cysts (trophozoites destroyed by gastric activity)
Often associated with drinking contaminated water (cysts can survive in water up to 3 months)
Incubation: 7-10 days
80
Giardia lamblia
*Etiology/Pathogenesis*
Symptoms: (3)
Symptoms:
- Acute onset of watery diarrhea
- Abdominal cramps, bloating and flatulence
- Some patients progress to chronic diarrhea with malabsorption (weight loss common)
81
Giardia lamblia
Identification of Organism: (3)
Microscoping examination of stool, duodenal aspiration or duodenal biopsy
Antigen testing for G.lamblia in the stool
String test (swallowing a string to obtain a sample from the upper part of the small intestine)
82
Cryptosporidium parvum
Basics:
Symptoms: Immunocompromised vs Immunocompetent
Basics: small coccidian protozoan parasite
Symptoms:
o Immunocompromised: severe, watery, prolonged diarrhea
o Immunocompetent: mild diarrhea
83
Cryptosporidium parvum
Life Cycle:
- What is ingested?
- What is released in intestine?
- What is shed in feces?
o Oocyst ingested in contaminated water
o Sporozoite released in intestine
o Sporozoite enters intestinal epithelial cells (infects the microvilli)
o Undergoes sexual and asexual replication
o Oocysts produced (infective stage) which are then shed in the feces
84
Microsporidia (Microspora):
Group of obligate intracellular, spore forming protists
85
Cyclospora cayetanesis:
How long does diarrhea last?
More severe in what type of patient?
Cyclospora cayetanesis: have cyanobacterium-like bodies
o Cause prolonged diarrhea (up to 7 weeks)
o More severe in AIDs patients
86
Isospora belli:
Clinically indistinguishable from:
Description of diarrhea:
Infects what part of intestine?
More severe in what type of patient?
Isospora belli: clinically indistinguishable from giardiasis, cryptosporidiosis and microsporodiosis
o Diarrhea without blood or leukocytes
o Infects entire intestine
o More severe in AIDS patients
87
Clostridium difficile is normal flora in what percent of people?
Normal flora in ~5% of healthy adults; can cause acute inflammation of the colonic mucosa in some cases
88
Clostridium difficile
| 2 Exotoxins produced:
Toxin-A Enterotoxin
| Toxin-B Cytotoxin
89
Clostridium difficile
Toxin-A Enterotoxin
Causes accumulation of:
Chemotactic for:
What does cell lysis cause the release of?
Toxin-A Enterotoxin: causes accumulation of viscous, bloody fluid
Chemotactic for PMNs, resulting in cell lysis
Cell lysis causes release of inflammatory mediatiors, which causes:
- Fluid secretion
- Altered membrane permeability
- Hemorrhagic necrosis of mucosa
90
Clostridium difficile
Toxin B Cytotoxin
Disrupts:
Decreases:
What is it similar to?
Disrupts the actin polymerization and cytoskeletal architecture
Decreases cellular protein synthesis (similar to diphtheria toxin)
91
Clostridium difficile
Source:
Cause of Diarrhea:
Source: endogenous or from the environment (nosocomial infections)
Cause of Diarrhea: altered intestinal flora from a course of antibiotics (antibiotic associated colitis)
Symptoms: variable
Asymptomatic carrier
Mild diarrhea
92
Pseudomembranous colitis:
Pseudomembranes/plaques consist of fibrin, mucus, necrotic epithelial cells, and leukocytes adherent to the underlying inflamed mucosa
93
Clostridium difficile
Identification
Characteristics:
Selective Media:
Tests:
Characteristics: spore forming, anaerobic, Gram positive rod
Selective Media: CCFA (cycloserine, cefoxitin, fructorse agar); culturing organism not helpful
Tests: toxin tests in stool are the most useful clinically (EIA test)
94
Enterohemorrhagic E.Coli (EHEC)
AKA:
Causes:
Also called Shiga-toxin E.coli (STEC) or Verocytotoxin E.Coli (VTEC)
Causes: diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS)
95
Enterohemorrhagic E.Coli (EHEC)
Adhesins
Bind to:
Mediated by: (2)
Tight binding to mucosal cells
| Mediated by Tir and intimin
96
Enterohemorrhagic E.Coli (EHEC)
| Virulence Factors: (3)
Adhesins
Shiga Toxins
Type III Secretion
97
Enterohemorrhagic E.Coli (EHEC)
```
Shiga Toxin
aka:
Type of toxin:
What does B subunit bind?
What does A modify? Block?
```
Shiga Toxin: AB type toxin (aka Shiga-like or Vero toxin)
B subunit binds Gb3 ganglioside on host cell
A subunit enzymatically modifies 28S ribosomal RNA of the 60S-ribosomal subunit
- Blocks proteins synthesis
- Eventually leads to cell death
98
Enterohemorrhagic E.Coli (EHEC)
Shiga Toxin causes:
Leads to:
Capillary thrombosis and associated inflammation of the colonic mucosa (leads to hemorrhagic colitis)
99
Enterohemorrhagic E.Coli (EHEC)
Shiga Toxin types:
Encoded by:
Types: strains may carry one or both; encoded by bacteriophages
Shiga Toxin I (StxI)
Shiga Toxin II (StxII)
100
Enterohemorrhagic E.Coli (EHEC)
| Type III Secretion:
Inserts toxin and its own receptor into the host cell; causes attaching and effacing lesions like EPEC
101
Enterohemorrhagic E.Coli (EHEC)
Cause:
Outbreaks occur from what?
How many organisms are needed for infection?
Incubation period:
Shiga-toxin producing strains colonize the intestinal tract of cattle and other farm animals
Outbreaks occur from contaminated meat (hamburger), milk and apple cider
Only a small number of organisms required for infection
Incubation Period: 3-4 days
102
Enterohemorrhagic E.Coli (EHEC)
Symptoms (4):
Symptoms:
Severe, crampy abdominal pain
Copious watery diarrhea that develops into grossly bloody diarrhea
Little to no fever*
Hemolytic Uremic Syndrome
103
Enterohemorrhagic E.Coli (EHEC)
Hemolytic Uremic Syndrome
What percent of patients?
Results in:
Caused by:
Hemolytic Uremic Syndrome: develops in 5-10% of patients (esp. young kids)
Acute renal failure, thrombocytopenia and hemolytic anemia
Caused by Shiga toxin damage to endothelial cells of renal glomeruli
104
Enterohemorrhagic E.Coli (EHEC)
Serotyping (3):
O Antigens: outer region 1 of LPS (endotoxin) polysaccharide Ag
H Antigens: flagella proteins
K Antigens: extracellular polysaccharide Ags
105
What causes 50-80% of EHEC infections?
What does it not ferment?
Serotype O157:H7: causes 50-80% of infections
Does not ferment sorbitol (almost all other strains do), therefore can be identified with MacConkey agar.
However, sorbitol positive strains may also produce Shiga toxins
106
Enterohemorrhagic E.Coli (EHEC)
Other Methods of identification: (3)
Anti-O157:H7 serum
Demonstrate cytotoxicity with Vero Cells
DNA probe for detection of Shiga toxin genes
107
What produces bacillary dysentery?
Shigella
Basics: produces bacillary dysentery (blood and mucus in stool)
108
Shigella
Virulence Factors: (5)
```
Invasion
Type III Secreation
Actin-Based Motility
Bacillary Dysentery
Shiga Toxin
```
109
Shigella
Invasion
Enters through:
Deep or superficial?
Invasion: enters through M cells only
Superficial: very rare penetration beyond mucosa
110
What is the primary virulence characteristic of Shigella?
Invasiveness
111
Shigella
Type III Secretion
What does actin rearrangement cause?
Used to induce actin rearrangements causing pseudopods at the basolateral surface of epithelial cells in order to take up bacteria
112
Shigella
Actin-Based Motility
What happens once the bacterium is in the cell?
Actin-Based Motility: once in the cell, causes rapid polymerization and depolymerization of actin at one pole, causing the bacteria to be propelled through the cell to invade adjacent ones
113
Shigella
What happens to invaded cells?
What is the result?
Invaded cells die and slough off (surface erosion of gut wall)
Results in the formation of shallow ulcers (ulcerative colitis)
114
Shigella
Bacillary Dysentery definition:
What causes damage to the epithelium, allowing more invasion by bacteria?
Bacillary Dysentery: local inflammation with abundant neutrophils, RBCs and mucus in the stool
Shigellae promotes cytokine release and an inflammatory response to cause damage to the epithelium, allowing more invasion by bacteria
115
What species of shigella produces shiga toxin?
| What does it play a role in?
Shiga Toxin: one species (S.dysenteriae type 1) produces Shiga toxin; plays a role in local destruction of the mucosa in this case
116
Shigella
Spread:
How infectious?
Spread: only human to human (by food, fingers, feces, and flies)
Highly Infectious: only need <1000 organisms for infection
117
Shigella
Four Serotypes:
Group A:
Group B:
Group C:
Group D:
Group A: S.dysenteriae (Shiga bacillus- largest producer of toxin)
Group B: S.flexneri* (causes the rest of US cases)
Group C: S.boydii
Group D: S. sonnei* (causes 60-80% of US cases)
118
Shigella
Disease:
Organisms multiply in the lumen of the small intestine, with higher numbers occurring in the lower intestine
119
Shigella
First 12 Hours:
12-72 Hours:
First 12 Hours: abdominal pain, cramping, and fever (while bacteria localized in SI)
12-72 Hours:
- Organism no longer detectable in upper intestine
- Fever decreases
- Pain becomes more severe (localizes to lower quadrants)
- Dysentery develops (cramps, tenesmus and lethargy)
- Bloody, low volume diarrhea with large number of PMNs in mucoid stool
120
Shigella
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Identification of Organism
Motile?
G +/-?
Lac +/-?
Ox +/-?
Serological identification
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o Basics: non-motile, Gram negative bacillus
o Lab Tests: lactose negative, oxidase negative
o Serological identification of serogroups
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Enteroinvasive E.Coli (EIEC)
Basics:
Virulence Factors
- Behaves like:
- Infects and spreads similar to:
Basics: relatively rare
Virulence Factors
o Behaves like Shigella (no Shiga toxin)
o Infects and spreads cell-to-cell similar to Shigella
122
Salmonella
Found in what species?
Exceptions:
Found in almost all animal species
Exceptions: some found in only humans (S.typhi)
123
Salmonella
| Virulence Factors: (3)
Adherence and Invasion
Type III Secretion
Endotoxin
124
Salmonella
Adherence and Invasion
Binds and invades what?
What happens inside the cell?
Organism binds microvilli and can invade M cells or epithethial cells
Bacteria engulfed in a vesicle (remain inside the phagosome and replicate)
125
Salmonella
Type III Secretion
What leads to ruffling and bacterial-mediated endocytosis?
Extensive actin rearrangement where the bacteria attaches leads to ruffling and "bacterial-mediated endocytosis"
126
Salmonella
Endotoxin
What is released upon lysis?
What happens because of this?
Lipid A of LPS released upon lysis
Induces inflammatory response that contributes to mucosal damage
127
Salmonella
Transmission:
How many Serotypes?
Not as infectious as:
Transmission: usually by contaminated food (poultry meat or eggs)
Many Serotypes: over 2400 based on O and H Ags
Not as infectious as Shigella: requires a large inoculum for infection
128
Salmonella
Causes 3 main clinical syndromes
Gastroenteritis (Enterocolitis)
Bacteremia
Enteric (Typhoid) Fever
129
Salmonella
Gastroenteritis (Enterocolitis)
*Incubation Period*:
Onset:
Fever:
Incubation Period: 8-48 hours
Onset: abrupt
Fever: usually low
130
Salmonella
Gastroenteritis (Enterocolitis)
Duration:
*GI Symptoms*:
Blood Culture:
Stool Culture:
Duration: 2-5 days
GI Symptoms: N/V/D at onset
Blood Culture: negative
Stool Culture: positive for several weeks
131
What is the most common form of Salmonella infection?
Gastroenteritis (Enterocolitis)
132
Salmonella
Bacteremia
Rare event that sometimes develops after gastroenteritis; secondary infection can occur
133
Salmonella
Bacteremia
*Incubation Period*:
Onset:
Fever:
Incubation Period: variable
Onset: abrupt
Fever: rapid rise and spike (septic)
134
Salmonella
Bacteremia
Duration:
*GI Symptoms*:
Blood Culture:
Stool Culture:
Duration: variable
GI Symptoms: often absent
Blood Culture: positive during fever
Stool Culture: infrequently positive
135
Salmonella
Enteric (Typhoid) Fever
Classically associated with:
Classically associated with S.typhi or S.paratyphi (others may also cause)
136
Salmonella
Enteric (Typhoid) Fever
*Incubation Period*:
Onset:
Fever:
Incubation Period: 7-20 days
Onset: insidious (gradual)
Fever: gradual, and then high plateau
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Salmonella
Enteric (Typhoid) Fever
Duration:
*GI Symptoms*:
Blood Culture:
Stool Culture:
Duration: several weeks
GI Symptoms: constipation early; bloody diarrhea late
Blood Culture: positive in 1-2 weeks of disease
Stool Culture: negative early; positive after 2 weeks
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Salmonella
Other Symptoms
Early:
Late:
Maculopapular Rash:
Early: chills, headache, anorexia, weakness and muscle aches
Late: fever, swollen LNs, enlargement of the liver and spleen
Maculopapular Rash (Rose Spots): 1/3 of patients get this on lower trunk
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Campylobacter
Virulence Factors (3):
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Flagella
Toxins
Protein S
140
Campylobacter
| Flagella:
Flagella: motility through mucus layer of SI (multiplies in the mucus layer)
141
Campylobacter
Toxins (3):
Effects on intestinal cells:
Toxins: enterotoxin, endotoxin (LPS) and cytotoxin destroys intestinal cells (bloody diarrhea)
142
Campylobacter
Protein S:
Blocks:
Causes what?
Protein S: surface protein functioning as a capsule
Blocks complement binding
Causes serum resistance to phagocytosis
143
Campylobacter
Infective Dose:
Transmission:
Incubation Period:
Infective Dose: 500-1,000,000
Transmission: most commonly associated with eating chicken (milk, water and other meats have also been implicated)
Incubation Period: 1-7 days
144
Campylobacter
Symptoms: (4)
Fever and malaise
Abdominal pain and cramps
Profuse watery or bloody diarrhea (due to mucosal inflammation)
PMNs in the stool
145
Guillan-Barre Syndrome
How long after infection?
Why does demyelination occur?
How long does it take to recover?
Guillan-Barre Syndrome: auto-immune mediated attack on nerve tissue 1-3 weeks following infection
Demyelination occurs due to similarities between host myelin and the surface of Campylobacter organism
Takes months to recover
146
Campylobacter
Motile or non-motile?
Spore forming?
Ox +/-?
What is characteristic in the stool sample?
Basics: motile, non-spore forming, comma-shaped Gram negative bacillus
Lab Tests: oxidase positive
Stool Sample: characteristic darting motility of organism
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Campylobacter
MacConkey Agar:
Incubation temp?
O2 and CO2 for incubation
Culture: selective media (will not grown on MacConkey even though it is Gram negative)
- Incubate at 42 degrees C
- Microaerophilic and capnophilic
148
Vibrio parahemolyticus
Basics:
Where is it a major problem?
Invades what?
Produces what?
Basics: halophilic (grows in brackish water) and contaminates seafood; major problem in Japan
Invasion: invades intestinal cells
Virulence: produces heat stable cytotoxin
149
Yersinia enterocolitica
Carriage:
Transmission:
Carriage: carried by livestock (mainly pigs), rabbits and rodents
Transmission: contaminated food, water or blood products
150
Yersinia enterocolitica
Enterocolitis (Most Common)
Effects:
What happens after invasion of terminal ileum?
What can it mimic?
Enterocolitis (Most Common):
Bloody diarrhea, fever and abdominal pain (1-2 weeks; due to necrosis of Peyer’s patches)
Mesenteric lymphadenitis (after invasion of terminal ileum; can cause abscesses and can mimic acute appendicitis; most common in young kids)
151
Yersinia enterocolitica
Transfusion Related Septicemia:
Grows at lower temperatures and can multiply to toxic levels in refrigerated blood stored for several weeks
152
Entamoeba histolytica (Amebic Dysentery)
Virulence Factors: (4)
What is the infectious stage of the life cycle?
How does it adhere to the luminal surface?
What are proteolytic enzymes involved in the dissolution of?
Life cycle: cyst stage (infectious stage; environmentally resistant) and trophozoite stage (invasive in the tissue)
Galactose-Specific Adhesion: adheres to luminal surface by galactose-inhibitable surface protein
Proteolytic Enzymes: involved in the dissolution of extracellular matrix that anchors cells in tissue structure
Cytolytic Enzymes
153
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Entamoeba histolytica (Amebic Dysentery)
Transmission:
```
Cyst is ingested, and its wall breaks down in the SI; trophozoites form from the nuclei and cytoplasm of the cyst (colonize the colon)
154
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Entamoeba histolytica (Amebic Dysentery)
Disease process
```
When does it begin?
Where does erotion of mucosa begin?
What can happen to ulcers?
How are amebic liver abscesses formed?
Disease Process: begins upon invasion of mucosal surface
Erosion of mucosa begins at base of the crypts and progresses to ulceration
Ulcers can extend into the submucosa to produce flask shaped lesions
Although rare, trophozoites can also enter the venules in the colon wall to be carried to extraintestinal sites (most commonly the liver- causing amebic liver abscess)
155
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Entamoeba histolytica (Amebic Dysentery)
Identification:
```
Microscopic examination of stool or colonoscopic sample
- Irregular shedding of organisms in stool
- Identification based on characteristic ultra-structure of cyst and/or trophozoite
156
What is the major etiological agent of chronic gastritis and peptic ulcers?
Helicobacter pylori:
Basics: major etiological agent of chronic gastritis and peptic ulcers; major risk factor for gastric cancer
90% of duodenal and 70-80% of gastric ulcers
157
Helicobacter pylori
Virulence Factors:
Urease
Flagella
Cytotoxin and Mucinase
158
Helicobacter pylori
Urease
Converts what to what?
What does this do for H.pylori?
Converts urea to ammonia and CO2; protects it from stomach acid (allows bacteria to establish in the mucin layer in the stomach)
159
Helicobacter pylori
| Flagella:
Allow rapid penetration of the gastric mucus
160
Helicobacter pylori
Cytotoxin and Mucinase
Localized destruction of tissue; stimulate infiltration of inflammatory cells
161
Helicobacter pylori
Pathogenesis
What type of gastritis?
Penetrates?
Adheres to?
Chronic type B gastritis (superficial and atrophic) with possible progression to adenocarcinoma
Penetrates the mucus layer of the host and adheres to the gastric mucosa
162
Helicobacter pylori
Identification
G+/-?
Shape:
Gastric biopsy:
Special media:
Basics: Small Gram negative curved bacillus
Gastric Biospy: culture or urease test (CLO test)
Special Media: enriched in 6-8% O2 (microaerophilic); incubate at 37 degrees C for 3-7 days
163
Helicobacter pylori
Pathogenesis
How does it produce ammonia?
How does it form an ulcer?
What could happen if allowed to perpetuate?
Produces ammonia using urease to neutralize gastric acid
Proliferate, migrate and finally form infectious focus; Results in development an ulcer by destruction of mucosa, inflammation and cell death
Increase secretion of gastrin and gastric acid stimulated by infection promotes gastric metaplasia
164
Listeria monocytogenes
| Basics:
Basics: usually only cause infections in immunocompromised
165
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Listeria monocytogenes
Virulence Factors (4):
```
Internalin
Listeriolysin O (LLO)
Actin Mediated Motility
Lipoteichoic Acid (LTA)
166
Listeria monocytogenes
Virulence Factors
Internalin
What type of protein?
Induces what process?
What does this help the intracellular pathogen avoid?
Internalin: bacterial surface protein that induces phagocytosis (intracellular pathogen can then avoid Ab-mediated defenses)
167
Listeria monocytogenes
Virulence Factors
What does LLO enable bacteria to do?
Listeriolysin O (LLO): enables bacteria to escape from phagosome and avoid intracellular killing
168
Listeria monocytogenes
Virulence Factors
Actin Mediated Motility
What does it allow the organism to do? Avoid?
Actin Mediated Motility: enables the organism to spread from cell to cell (avoid Abs, complement and neutrophils)
169
Listeria monocytogenes
Virulence Factors
LTA causes:
Lipotechoic Acid (LTA): causes septic shock
170
Listeria monocytogenes
```
Where is it found?
What is notable about it?
Where is it found?
What are the highest rates found?
Incubation period:
```
Ubiquitous: found in soil, decaying vegetation and fecal flora of many animals
Only pathogenic Listeria species in humans
Cause: most human infection is from food (raw vegetables, raw milk, soft cheeses, fish, poultry, and meats)
Immunocompromised: highest infection rates seen in infants, pregnant women (~30% of all cases) and other immunocompromised individuals
Incubation Period: 11-70 days (mean ~1 month)
171
Listeria monocytogenes
Disease Process
Where does it cross the mucosal barrier?
What happens in healthy people?
Immunocompromised?
What can it cause?
Crosses the mucosal barrier through M cells in the intestine and enters the bloodstream
Healthy People: cleared by macrophages
Immunocompromised: hematogenous dissemination can occur to any site (particularly the CNS and placenta)
Can cause meningitis and still births/birth defects
172
Listeria monocytogenes
Identification
```
G +/-?
Anaerobic?
Spore-forming?
Motility:
Ox +/-?
Cat +/-?
What type of hemolysis?
```
Basics: Gram positive, facultative anaerobe, non-spore forming, tumbling motility at room-temperature, non-motile at 37 degrees C
Lab Tests: oxidase negative, catalase positive, beta-hemolytic
173
What organisms cause disease with preformed toxins? (3)
C.botulinum, S.aureus, B.cereus
174
What organisms cause disease with toxin formed in the intestine? (5)
V.cholerae, E.coli (ETEC, EHEC), B.cereus, C.perfringens
175
What organisms cause disease by invasion? (6)
Salmonella, Shigella, Yersinia enterocolitica, Campylobacter, Listeria, V.parahemolytica
176
Nematodes (Round Worms): (3)
* Ascaris lumbricoides
* Enterobius vermicularis (pinworm)
* Ancylostoma duodenale and Necator americanus (hookworms)
177
Ancylostoma duodenale and Necator americanus (hookworms)
Infects what percent of the world population?
What type is found in the tropics and North America?
Temperate zones?
Infects 24% of the world’s population
Necator: worldwide tropics and North America
Ancylostoma: temperate zones
178
Ascaris lumbricoides
How common worldwide?
Transmission:
Where do adults live?
What organ do the larvae pass through?
Very common: found world wide
Transmission: eating viable eggs from feces-contaminated soil or food
Disease Process:
o Adults live in lumen of SI
o Larvae pass through lungs
179
Ascaris lumbricoides
Symptoms
Low Infestation:
High Infestation:
Low Infestation: asymptomatic in most; can also cause GI upset, colic and loss of appetite
Heavy Infection: adult worms ball up in SI and result in physical obstruction
180
What is the most common helminth?
Enterobius vermicularis (pinworm)
- Found worldwide
- Mainly in children
181
Enterobius vermicularis (pinworm)
Transmission:
Where does the adult live?
When does the female deposit eggs? Where? What does this lead to?
Transmission: fecal-oral route (most common in children)
Disease Process:
o Adult lives in cecum
o Female deposits eggs at night in the perianal area, leading to perianal pruritis (severe itching)
182
Ancylostoma duodenale and Necator americanus (hookworms)
Transmission:
Where does the adult live?
What organ do the larvae pass through?
How much blood can each worm withdraw
Transmission: through the skin from infected soil or from drinking contaminated water
Disease Process:
o Adult lives in small intestines
o Larvae pass through the lungs
o Each worm can withdraw up to 0.2ml of blood/day
183
Cestodes (Tapeworms): (2)
```
Taenia saginata (Beef Tapeworm)
Taenia solium (Pork Tapeworm)
```
184
Taenia saginata (Beef Tapeworm)
Distribution:
What organ does it inhabit?
Adult length:
Transmission:
Worldwide distribution
Basics: inhabits the small intestine; adult is 3-10 meters in length
Transmission: occurs by eating uncooked beef
185
Taenia solium (Pork Tapeworm)
Distribution:
What organ does it inhabit?
What is cysticeorocosis? What causes it?
Transmission:
Worldwide distribution
Basics: inhabits small intestine; can invade gut wall and migrate to various tissues (such as muscles or brain, causing cysticeorocosis)
Transmission: occurs by eating uncooked pork
