Gastrointestinal Infections Flashcards
1
Q
What are the 3 elements of the intestinal mucosal barrier?
A
Physical
Biochemical
Immunological
2
Q
What are the 3 components of the physical intestinal mucosal barrier?
A
Mucous
Intestinal epithelium
Microbiota
3
Q
What are the 4 components of the biochemical intestinal mucosal barrier?
A
Bile and gastric acid
Defensins
Lysozyme
Reg3gamma
4
Q
What are the 3 components of the immunological intestinal mucosal barrier?
A
Antimicrobial peptides
Secretory IgA
Cellular immunity
5
Q
What are factors that can compromise the function of the gastrointestinal tract?
A
Diet Antibiotics Immune suppressants Cancer or radiation therapy Anatomic alterations Host genetics Ingestion of preformed toxins or microorganisms
6
Q
What are the 3 categories of gastrointestinal tract infections?
A
Diarrhoeal diseases
Acute enteric infections
Non-diarrhoeal gastrointestinal infections
7
Q
What category of gastrointestinal tract infection does Salmonella enterica (typhi and paratyphi) cause?
A
Acute enteric infection
8
Q
What category of gastrointestinal tract infection does non-typhoidal Salmonella enterica cause?
A
Acute enteric infection
9
Q
What category of gastrointestinal tract infection does Enteropathogenic E. coli (EPEC) cause?
A
Acute enteric infection
10
Q
What category of gastrointestinal tract infection does Enterohemorrhagic E. coli (EHEC) cause?
A
Acute enteric infection
11
Q
What category of gastrointestinal tract infection does intestinal protozoal infection cause?
A
Acute enteric infection
12
Q
What category of gastrointestinal tract infection does Clostridium difficile cause?
A
Acute enteric infection
13
Q
What category of gastrointestinal tract infection does acute gastritis and peptic ulcer disease come under?
A
non-diarrhoeal infection
14
Q
What category of gastrointestinal tract infection does acute cholecystitis come under?
A
non-diarrhoeal infection
15
Q
What category of gastrointestinal tract infection does acute peritonitis come under?
A
non-diarrhoeal infection
16
Q
How are gastrointestinal tract infections transmitted?
A
Food Water person-to-person animal-to-person fomites
17
Q
What is a localised gastrointestinal tract infection?
A
Infection stays at mucosal site of GI tract, within epithelial cells or resident immune cells
18
Q
What is an invasive gastrointestinal tract infection?
A
Mucosal barrier is compromised, epithelial and immune cells are actively invaded and pathogen disseminated to organs. Can re-seed into GI tract
19
Q
What are the main manifestations/symptoms of GI infection?
A
Diarrhoea
Nausea
Vomiting
Abdominal cramping
20
Q
How many cases of diarrhoea per year?
A
1.7-5 billion
21
Q
What is diarrhoea?
A
It is unformed, liquid faeces
It is the result of increase in fluid, loss of electrolytes in lumen of gut
Method by which host expels pathogen
22
Q
What is acute diarrhoea?
A
<14 days, very common, abnormally frequent semi-solid or fluid faecal matter discharge from the bowel.
Caused by GI infection
23
Q
What is persistent diarrhoea?
A
> 14 days. some GI infections can cause this
24
Q
What is chronic diarrhoea?
A
> 4 weeks, usually outcome of an intestinal disease or disorder, such as Celiac or Crohn’s disease
25
What are the 4 types of diarrhoea?
Secretory
Exudative
Inflammatory
Dysentry
26
What is secretory diarrhoea?
Increase in the active secretion or
inhibition of absorption
No structural damage
Can be caused by cholera
27
What is exudative diarrhoea?
Occurs in inflammatory bowel disease such as Crohn's or ulcerative colitis and other severe infections such as E. coli or food poisoning
Stool contains blood and pus
28
What is inflammatory diarrhoea?
Damage to mucosal lining, leading to passive loss of protein-rich fluids and a decreased ability to absorb these lost fluids
Can be caused by bacterial, viral or parasitic infections
Can be autoimmune
Can be tuberculosis, colon cancer and enteritis
29
What is dysentery diarrhoea?
Visible blood in the stool as a result of bowel tissue invasion
Often a result of Shigella, Entamoeba histolytica or Salmonella
30
What is the 3rd leading cause of death in children under 5?
Diarrhoea
31
What are the 4 main causes of diarrhoea in developing countries?
Rotavirus
E. coli
Cryptosporidum spp.
Shigella spp.
32
What are the 5 main causes of diarrhoea in developed countries?
```
Norovirus
E. coli
Campylobacter
Salmonella
Shigella spp.
```
33
What are the 6 distinct E. coli pathotypes that cause diarrhoea?
```
EPEC
EHEC
ETEC
EAEC
EIEC
DAEC
```
34
What is EPEC?
Enteropathogenic E. coli
35
What is EHEC?
Enterohaemorrhagic E. coli
36
What is ETEC?
Enterotoxigenic E. coli
37
What is EAEC?
Enteroaggregative E. coli
38
What is EIEC?
Enteroinvasive E. coli
39
What is DAEC?
Diffuse-aggregative E. coli
40
What type of bacteria is Enterobacteriaceae?
Gram negative bacillus
41
```
EHEC
Cause
Incubation period
Disease duration
Manifestations
Transmission
Diagnosis
Treatment
Virulence Factors
```
Cause: enterobacteriaceae
Incubation: 3-4 days
Duration: 5-10 days
Manifestions: blood diarrhoea, can cause haemolytic uremic syndrome
Transmission: undercooked meat or fresh vegetables, human-to-human, faecal oral route
Diagnosis: stool culture, PCR for toxins and virulence factors
Treatment: hydration, dialysis for HUS, NO antibiotics unless persistent
Virulence factors: Type III secretion system, shiga toxin(Stx), cytotoxic to renal endothelial cells, resulting in acute renal failure
42
What is HUS?
Haemolytic uremic syndrome
43
```
ETEC
Cause
Incubation period
Disease duration
Manifestations
Transmission
Diagnosis
Treatment
Virulence Factors
```
Cause: Enterobacteriaceae
Incubation: 1-7 days
Duration: 2-6 days
Manifestations: watery diarrhoea (Traveller's diarrhoea) in children, adults and pigs
Transmission: food or water contaminated with faeces
Diagnosis: Stool culture, PCR for toxins and colonisation factors
Treatment: hydration, antibiotics not usually required
Virulence factors: colonisation factors (CFs) -> fimbrial adhesins called pili
Produces enterotoxins (heat-labile and heat-stable), plasmid encoded
44
Compare and contrast ETEC and EHEC
```
ETEC
Low-income
children and travellers at risk
infectious dose 10^6-10^30 bacteria
incidence 2.7%
reservoir humans
Acute watery diarrhoea
EHEC
high-income
children and elderly at risk
infectious dose 50-100 bacteria
incidence 0.04%
reservoir cows and sheep
bloody diarrhoea
```
45
What causes watery diarrhoea in ETEC?
1. ETEC adheres to mucous layer
2. Mucinase degrades mucous layer
3. ETEC produces enterotoxins
4. ETEC enters epithelial cells
5. CFTR is activated
6. Extracellular water and chloride ions increase
46
How does EHEC cause blood diarrhoea?
1. EHEC attaches and effaces epithelial cells
2. EHEC produces Shiga toxin
3. EHEC causes apoptosis of epithelial cell
4. EHEC translocates to the lamina propria
5. EHEC causes macrophage apoptosis causing the secretion of cytokines
6. Shiga toxin disseminates into the blood stream causing systemic dissemination
47
What are the two types of Salmonella enterica?
Typhoidal
| Non-typhoidal
48
Typhoidal Salmonella enterica
Host
Diseases and which serovars cause it
Human-specific, invasive
Typhoid fever: S. Typhi
Paratyphoid fever: S. Paratyphi A, B or C
49
Non-typhoidal Salmonella enterica
Host
Most common serovars
```
Mammals, reptiles and birds
S. enteritidis
S. Typhimurium
S. Newport
S. Javiana
```
50
```
Non-typhoidal Salmonella enterica
Cause
Incubation
Duration
Manifestations
Transmission
Diagnosis
Treatment
```
Cause: Enterobactericeae
Incubation: 6-72 hours
Duration: 4-7 days
Manifestations: self-limiting acute gastroenteritis with nausea, vomiting and non-blood diarrhoea
fever and cramps may occur
Transmission: food or water contaminated with faeces
direct contact with infected animal/human
Diagnosis: isolation from stool culture, PCR
Treatment: hydration, antimicrobials can prolong shedding so not recommended except for severely ill patients and people at risk of invasive diseases
51
Describe Salmonella pathogenesis
It has 2 Type III secretion systems, SPI-1 and SPI-2
SPI-1 is inserted into the host cell membrane from the extracellular space, injecting SPI-1 effectors into the cell
SPI-2 is inserted into the vacuole membrane from inside the vacuole, injecting SPI-2 effectors into the cell
52
What is the host of Typhimurium Salmonella enterica?
poultry and pigs
53
What is the host of Enteritidis Salmonella enterica?
poultry
54
What is the host of Dublin Salmonella enterica?
cattle
55
What is the host of Newport Salmonella enterica?
cattle
56
What is the host of Choleraesius Salmonella enterica?
pigs
57
```
Shigella
Cause
Incubation
Duration
Manifestations
Transmission
Diagnosis
Treatment
Virulence factors
```
Cause: enterobacteriaceae
Incubation: 1-7 days
Duration:4-7 days
Manifestations: diarrhoea, fever, nausea, vomiting and abdominal cramps
Stool has blood, mucous and pus although some people may have watery diarrhoea
complications include toxic megacolon and reactive arthritis
Transmission: Humans, faecal-oral route
May be spread by contaminated food, water, or by flies
Diagnosis: stool culture, PCR serotyping, AMR profiling
Treatment: hydration, antibiotics are REQUIRED ALWAYS
Virulence: Type III secretion, large virulence plasmid, toxins
58
What are the 4 species of Shigella?
Group A: S. dysenteriae (most severe)
Group B: S. flexneri (most common cause of shigellosis)
Group C: S. boydii
Group D: S. sonnei
59
What cells does Shigella invade?
Epithelial cells and macrophages
60
What disease does Shigella cause?
Inflammatory colitis -> Shigellosis
61
Where does cell to cell movement of Shigella occur?
Tricellular junctions via clathrin-dependent endocytosis
62
What type of diarrhoea is Shiga toxin associated with?
Bloody diarrhoea
63
What does Shiga toxin cause?
cell stress responses
Cell death
Inhibits protein synthesis
Activates immune responses leading to inflammation
64
What species of Shigella was first found to produce Shiga toxin?
S. dysenteriae
65
What are 3 gram-positive bacterial agents that cause food poisoning?
Staphylococcus aureus
Clostridium perfringens
Bacillus cereus
66
How does Staph. aureus cause food poisoning?
Enterotoxins A-E, heat stable
Effect on CNS causes severe vomiting with 30minutes-8hours of consumption
Diarrhoea not always present, recovery within 24 hours
67
How does C. perfringens and B. cereus cause food poisoning?
Produce enterotoxins, spore-contaminated food
Diarrhoeal disease
Undercooked food
B. cereus ubiquitous in soil, can cause diarrhoea from enterotoxin production in the gut OR vomiting due to ingestion of toxin in food
Culture and PCR, antibiotics not indicated
68
What foods in B. cereus infection are most likely to lead to vomiting?
Rice and pulses
69
Which strain of enterotoxin in S. aureus is most common?
A
70
What type of bacteria is Listeria monoctyogens?
gram positive coccobacillus
non-spore forming
highly motile with peritrichous flagella
71
What GI disease does Listeria monocytogenes cause?
Food poisoning, Listeriosis
72
```
Listeriosis
Cause
Transmission
What it does in GI
Population at risk
Manifestations
treatment
```
Cause: Listeria monocytogenes
Transmission: uncooked foods, (pate, milk, soft cheese, coleslaw, melons, frozen vegetables and berries)
What it does: adheres to intestinal mucosa and invades cell
Population at risk: pregnant women, immunocompromised, elderly
Manifestations: asymptomatic in healthy adults, can present as meningitis
Treatment: ampicillin combined with gentamycin
73
Pathogenesis of Listeriosis
1. Association with the host and internalisation
2. escape from primary vacuole
3. recruitment of host cell actin
4. cell to cell spread
74
Virulence factors of Listeria monocytogenes
```
Listeriolysin O and S (LLO and LLS)
ActA protein
Phospholipases
Internalins
Surface and chaperone proteins
Flagella
```
75
What barriers can Listeria monocytogenes cross?
Placental barrier
| Blood brain barrier
76
What happens in pregnancy if infected with Listeria monocytogenes?
Can cross the placental barrier
Can result in death of baby and survival of mother
Listeriosis typically occurs in third trimester
Invades placenta through phagocytosis by macrophages and then endothelial cells in the placenta and makes its way to the foetus
Causes premature labour or death of foetus
Treatment: ampicillin combined with gentamicin
77
What type of virus is Norovirus?
ssRNA virus
| Calciviridae
78
```
Norovirus
Incubation
Duration
Manifestations
Transmission
Diagnosis
Treatment
```
```
Incubation: 1-2 days
Duration: 2-4 days, self-limiting
Manifestations: initially nausea and cramping, followed by vomiting and diarrhoea
fever, headache, myalgia may occur
diarrhoea = adults
vomiting - children
Transmission: humans, faecal-oral
Diagnosis: PCR on faecal sample
Treatment: hydration, symptomatic relief of nausea, headache and myalgia, no antivirals available
```
79
Pathophysiology of Norovirus
Replicates in small intestine
Attachment receptors are histo-blood group antigens (HBGAs)
Some individuals may harbour inactivating mutation in FUT2, which leads to absence of ABO antigens and these individuals have lower susceptibility
Mouse norovirus is used as a model to study human norovirus
infection is influenced by host microbiome
80
Norovirus genome structure
```
Positive ssRNA
7.5kb
ORF1
ORF2
ORF3
ORF4
```
81
What does ORF1 of norovirus encode?
```
non-structural genes
NS3 (NTPase and helicase)
NS5 (VPg) aids in translation
NS6 (protease) and NS7 (RdRp)
Localise with replication complex
```
82
What does ORF2 of norovirus encode?
major capsid 1
83
What does ORF3 of norovirus encode?
minor capsid 2
84
What does ORF4 of norovirus encode?
virulence factor
85
Norovirus Replication Cycle
Replicates in virus-induced membrane vesicles from the ER
dsRNA intermediate which acts as template
Viral replication can activate through the integrated stress response (ISR) through:
- PKR detecting viral dsRNA
- PERK detecting ER-stress
86
What type of virus is Rotavirus?
dsRNA virus
Reoviridae
9 species A-I
87
```
Rotavirus
Disease
Incubation
Duration
Manifestations
Transmission
Diagnosis
Treatment
```
Disease: gastroenteritis
Incubation: 1-3 days
Duration: 2-5 days
Manifestations: fever and vomiting 2-3 days, watery diarrhoea for 4-5 days
Transmission: faecal-oral, person to person, fomites, possibly airborne droplets
Diagnosis: PCR of stool or EIA of stool
Treatment: Hydration, restoration of electrolytes, no anti-viral available
Vaccine: rotarix (live attenuated) delivered orally 6-14 weeks of age
88
Is there a vaccine for rotavirus?
Yes, rotarix (live attenuated) delivered orally 6-14 weeks of age
89
Rotavirus Replication Cycle
1. attachment and internalisation
2. early endosome
3. uncoating
4. transcription
5. translation
6. DLP assembly
7. Replication
8. budding and transient enveloped particle
9. loss of envelope and particle maturation
10. lysis
90
Rotavirus pathogenesis
Viral replication is primarily limited to the villous epithelium of small intestine
The severity of diarrhoea correlates with degree of mucosal damage
Rotavirus has a non-structural protein (NSP4) which has enterotoxin-like activity in animal models
91
What are the types of Viral hepatitis and what transmission and carrier state?
```
A & E
transmitted faecal oral route
no carrier state
B, C & D
transmitted faecal oral route by blood contaminated equipment
sexually transmitted
chronic carrier stage
```
92
Are there vaccines for any of the types of hepatitis?
Yes for A & B and part of the immunisation schedule
93
What type of virus is hep A?
small, non-enveloped symmetrical, linear ssRNA virus
| picornaviridae
94
How does Hep A infect the GI tract?
Enters the blood from the GI tract, infects the liver and then the biliary tract
Virus replicates in liver
Large quantities of virus are shed in faeces during incubation period before onset of symptoms
95
```
Hep A
Incubation
Duration
Manifestations
Transmission
Diagnosis
Treatment
```
Incubation: 15-50 days
Duration: 2-6 months
Manifestations: fatigue, sudden nausea, vomiting, abdominal pain, discomfort near liver, clay-coloured bowel movements, loss of appetite, low-grade fever, dark urine, joint pain, jaundice, intense itching
Transmission: person to person, faecal-oral route
Exposure to contaminated food
Diagnosis: HAV-specific immunoglobulin M in serum, PCR or genotyping
Treatment: HAV vaccine available
Immunoglobulin can be used for pre and post exposure prophylaxis with HAV
96
```
Giardia lamblia
General
Incubation
Duration
Manifestations
Transmission
Diagnosis
Treatment
```
General: Hexamitidae. Infects small intestine, more common in infants, young children and young adults
Incubation:1-2 weeks
Duration: 7-10 days
Manifestations: abdominal cramping, bloating feeling a flatulence, profuse watery diarrhoea, stools may later become greasy and foul smelling
Transmission: faecal-oral, contaminated food or water, contaminated pools
Diagnosis: Antigen in stool by EIA, cysts and or trophozoites in stool by microscopy. Testing should occur over three days
Treatment: Antibiotics (metronidazole) 3 times daily for 5 days
97
Giardia lamblia lifecycle
Cysts are resistant forms and are responsible for transmission of giardiasis
1. cysts and trophozoites can be found in the faeces (diagnostic phases)
2. infection occurs by ingestion of cysts in contaminated water, food or by the faecal oral route
3. In the small intestine, each cyst produces two trophozoites
4. Trophozoites multiply, remaining in the lumen of the proximal small bowel, where they can be free or attached to the mucosa by a ventral sucking disk.
5. Encystation occurs as the parasites transit toward the colon
6. the cyst stage found most commonly in non-diarrhoeal faeces
98
```
Cryptosporidium
General
Incubation
Duration
Manifestations
Transmission
Diagnosis
Treatment
```
General: Cryptosporidiiae. Found in most habitats: animals, fish, mammals and reptiles. C. hominis and C. parvum most common in humans
Incubation:1-12 days
Duration: 1-2 weeks
Manifestations: gastroenteritis. enteric symptoms include watery diarrhoea associated with abdominal cramping and pain, dehydration, weight loss, fever, nausea and vomiting
Transmission: faecal-oral route
Outbreaks associated with: 1) contaminated drinking water, 2) contaminated swimming pools
Reservoirs include: humans and animals
May be found in soil, food and water, or on fomites contaminated with faeces
Diagnosis: Antigen detection with EIA
Oocyst detection in stool using immunofluorescent assay
oocyst detection in stool using modified Ziehl Neelsen test
Treatment: No anti-cryptosporidial drug
hydration and electrolyte therapy
99
What are the main causes of Cryptosporidium?
C. hominis
| C. parvum
100
Cryptosporidium in environment particularly water
Oocysts can survive for a long period of time in the environment and are resistant to chlorination especially is faecal contamination is present
Commercial water purification should include flocculation and filtration
101
Cryptosporidium and HIV/AIDS
Individuals infected with HIV/AIDS
- Extra-intestinal infection of the biliary and respiratory tracts may occur in patients with low CD4 counts
- HIV patients with a CD4 count of <150 have:
- ->chronic persisting diarrhoea with foul-smelling bulky stool
- ->weight loss and malabsorption
102
Which GI disease are notifiable in Australia?
```
Cryptosporidiosis
EHEC
Shiga toxin producing E. coli
Hep A
Hep E
Listeriosis
Salmonellosis
Typhoid fever
Shigellosis
```
103
Management of GI infections
Avoid drinking untreated water
Avoid eating undercooked meat or seafood
Keep chopping boards separate and sterilise often
Pregnant women should avoid foods likely to be contaminated with Listeria
Ensure day care utilise proper hygiene
Warn travellers of possible GI infection
Offer typhoid vaccine to travellers going to countries where typhoid fever is prevalent
Advise people to get the Hep A vaccine
