Gastrointestinal Infections Flashcards
What are the 3 elements of the intestinal mucosal barrier?
Physical
Biochemical
Immunological
What are the 3 components of the physical intestinal mucosal barrier?
Mucous
Intestinal epithelium
Microbiota
What are the 4 components of the biochemical intestinal mucosal barrier?
Bile and gastric acid
Defensins
Lysozyme
Reg3gamma
What are the 3 components of the immunological intestinal mucosal barrier?
Antimicrobial peptides
Secretory IgA
Cellular immunity
What are factors that can compromise the function of the gastrointestinal tract?
Diet Antibiotics Immune suppressants Cancer or radiation therapy Anatomic alterations Host genetics Ingestion of preformed toxins or microorganisms
What are the 3 categories of gastrointestinal tract infections?
Diarrhoeal diseases
Acute enteric infections
Non-diarrhoeal gastrointestinal infections
What category of gastrointestinal tract infection does Salmonella enterica (typhi and paratyphi) cause?
Acute enteric infection
What category of gastrointestinal tract infection does non-typhoidal Salmonella enterica cause?
Acute enteric infection
What category of gastrointestinal tract infection does Enteropathogenic E. coli (EPEC) cause?
Acute enteric infection
What category of gastrointestinal tract infection does Enterohemorrhagic E. coli (EHEC) cause?
Acute enteric infection
What category of gastrointestinal tract infection does intestinal protozoal infection cause?
Acute enteric infection
What category of gastrointestinal tract infection does Clostridium difficile cause?
Acute enteric infection
What category of gastrointestinal tract infection does acute gastritis and peptic ulcer disease come under?
non-diarrhoeal infection
What category of gastrointestinal tract infection does acute cholecystitis come under?
non-diarrhoeal infection
What category of gastrointestinal tract infection does acute peritonitis come under?
non-diarrhoeal infection
How are gastrointestinal tract infections transmitted?
Food Water person-to-person animal-to-person fomites
What is a localised gastrointestinal tract infection?
Infection stays at mucosal site of GI tract, within epithelial cells or resident immune cells
What is an invasive gastrointestinal tract infection?
Mucosal barrier is compromised, epithelial and immune cells are actively invaded and pathogen disseminated to organs. Can re-seed into GI tract
What are the main manifestations/symptoms of GI infection?
Diarrhoea
Nausea
Vomiting
Abdominal cramping
How many cases of diarrhoea per year?
1.7-5 billion
What is diarrhoea?
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
What is acute diarrhoea?
<14 days, very common, abnormally frequent semi-solid or fluid faecal matter discharge from the bowel.
Caused by GI infection
What is persistent diarrhoea?
> 14 days. some GI infections can cause this
What is chronic diarrhoea?
> 4 weeks, usually outcome of an intestinal disease or disorder, such as Celiac or Crohn’s disease
What are the 4 types of diarrhoea?
Secretory
Exudative
Inflammatory
Dysentry
What is secretory diarrhoea?
Increase in the active secretion or
inhibition of absorption
No structural damage
Can be caused by cholera
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
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
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
What is the 3rd leading cause of death in children under 5?
Diarrhoea
What are the 4 main causes of diarrhoea in developing countries?
Rotavirus
E. coli
Cryptosporidum spp.
Shigella spp.
What are the 5 main causes of diarrhoea in developed countries?
Norovirus E. coli Campylobacter Salmonella Shigella spp.
What are the 6 distinct E. coli pathotypes that cause diarrhoea?
EPEC EHEC ETEC EAEC EIEC DAEC
What is EPEC?
Enteropathogenic E. coli
What is EHEC?
Enterohaemorrhagic E. coli
What is ETEC?
Enterotoxigenic E. coli
What is EAEC?
Enteroaggregative E. coli
What is EIEC?
Enteroinvasive E. coli
What is DAEC?
Diffuse-aggregative E. coli
What type of bacteria is Enterobacteriaceae?
Gram negative bacillus
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
What is HUS?
Haemolytic uremic syndrome
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
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
What causes watery diarrhoea in ETEC?
- ETEC adheres to mucous layer
- Mucinase degrades mucous layer
- ETEC produces enterotoxins
- ETEC enters epithelial cells
- CFTR is activated
- Extracellular water and chloride ions increase
How does EHEC cause blood diarrhoea?
- EHEC attaches and effaces epithelial cells
- EHEC produces Shiga toxin
- EHEC causes apoptosis of epithelial cell
- EHEC translocates to the lamina propria
- EHEC causes macrophage apoptosis causing the secretion of cytokines
- Shiga toxin disseminates into the blood stream causing systemic dissemination
What are the two types of Salmonella enterica?
Typhoidal
Non-typhoidal
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
Non-typhoidal Salmonella enterica
Host
Most common serovars
Mammals, reptiles and birds S. enteritidis S. Typhimurium S. Newport S. Javiana
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
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
What is the host of Typhimurium Salmonella enterica?
poultry and pigs
What is the host of Enteritidis Salmonella enterica?
poultry
What is the host of Dublin Salmonella enterica?
cattle
What is the host of Newport Salmonella enterica?
cattle
What is the host of Choleraesius Salmonella enterica?
pigs
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
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
What cells does Shigella invade?
Epithelial cells and macrophages
What disease does Shigella cause?
Inflammatory colitis -> Shigellosis
Where does cell to cell movement of Shigella occur?
Tricellular junctions via clathrin-dependent endocytosis
What type of diarrhoea is Shiga toxin associated with?
Bloody diarrhoea
What does Shiga toxin cause?
cell stress responses
Cell death
Inhibits protein synthesis
Activates immune responses leading to inflammation
What species of Shigella was first found to produce Shiga toxin?
S. dysenteriae
What are 3 gram-positive bacterial agents that cause food poisoning?
Staphylococcus aureus
Clostridium perfringens
Bacillus cereus
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
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
What foods in B. cereus infection are most likely to lead to vomiting?
Rice and pulses
Which strain of enterotoxin in S. aureus is most common?
A
What type of bacteria is Listeria monoctyogens?
gram positive coccobacillus
non-spore forming
highly motile with peritrichous flagella
What GI disease does Listeria monocytogenes cause?
Food poisoning, Listeriosis
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
Pathogenesis of Listeriosis
- Association with the host and internalisation
- escape from primary vacuole
- recruitment of host cell actin
- cell to cell spread
Virulence factors of Listeria monocytogenes
Listeriolysin O and S (LLO and LLS) ActA protein Phospholipases Internalins Surface and chaperone proteins Flagella
What barriers can Listeria monocytogenes cross?
Placental barrier
Blood brain barrier
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
What type of virus is Norovirus?
ssRNA virus
Calciviridae
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
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
Norovirus genome structure
Positive ssRNA 7.5kb ORF1 ORF2 ORF3 ORF4
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
What does ORF2 of norovirus encode?
major capsid 1
What does ORF3 of norovirus encode?
minor capsid 2
What does ORF4 of norovirus encode?
virulence factor
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
What type of virus is Rotavirus?
dsRNA virus
Reoviridae
9 species A-I
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
Is there a vaccine for rotavirus?
Yes, rotarix (live attenuated) delivered orally 6-14 weeks of age
Rotavirus Replication Cycle
- attachment and internalisation
- early endosome
- uncoating
- transcription
- translation
- DLP assembly
- Replication
- budding and transient enveloped particle
- loss of envelope and particle maturation
- lysis
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
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
Are there vaccines for any of the types of hepatitis?
Yes for A & B and part of the immunisation schedule
What type of virus is hep A?
small, non-enveloped symmetrical, linear ssRNA virus
picornaviridae
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
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
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
Giardia lamblia lifecycle
Cysts are resistant forms and are responsible for transmission of giardiasis
- cysts and trophozoites can be found in the faeces (diagnostic phases)
- infection occurs by ingestion of cysts in contaminated water, food or by the faecal oral route
- In the small intestine, each cyst produces two trophozoites
- 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.
- Encystation occurs as the parasites transit toward the colon
- the cyst stage found most commonly in non-diarrhoeal faeces
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
What are the main causes of Cryptosporidium?
C. hominis
C. parvum
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
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
Which GI disease are notifiable in Australia?
Cryptosporidiosis EHEC Shiga toxin producing E. coli Hep A Hep E Listeriosis Salmonellosis Typhoid fever Shigellosis
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
