Gastroenteritis and Waterborne Diseases Flashcards
Define gastroenteritis
Transient disorder due to enteric infection with viruses, bacteria or parasites
OR
Acute diarrhoeal disease of rapid onset with or without nausea
What are characteristics of gastroenteritis?
Sudden onset of diarrhoea with or without vomiting
Define acute diarrhoea
3 or more episodes of liquid/semi-liquid stool in 24hr period
Define prolonged diarrhoea
acute onset diarrhoea that has persisted for over 14 days
What is dysentery?
Acute infectious gastroenteritis characterised by diarrhoea with blood and mucus often with fever and abdominal pain
What is travellers diarrhoea?
Development of diarrhoea at the destination when travelling from high income to lower and middle income countries
At least 1 additional symptom eg. abdominal cramps, tenesmus, nausea, vomiting, fever, faecal urgency
What is antibiotic-associated diarrhoea?
Clinical infection when normal gut flora is disturbed by antibiotic use, allowing certain strains of Clostridium difficile to grow and produce toxins
What happens in gasteroenteritis?
Inflammation of stomach and intestines linings
How can GI tract infections be caused?
Mostly via:
Food and water
Contaminated environment
Direct close contact, e.g. sexual
Poor hygiene
Who is most affected by gastroenteritis?
Children < 5 years of age
Adults > 70 years of age
What investigations can be done for gastroenteritis?
Bacteriology
Virology
Parasitology
How is a stool sample investigated in the lab?
Look at it under microscope to possible see parasites
Can be cultured on various mediums to test for specific bacteria - XLD, SMAC, Campylobacter, selenite
Further biochemical tests can be done and sensitivity testing
What bacteria is the XLD medium for?
Shigella and salmonella
What bacteria is the SMAC medium for?
E coli O157
What bacteria is selenite medium for?
Salmonella
What parasites are commonly looked for in microscopy?
Giardia
Entameoba
Histolytica
Microsporidia
Cyclospora cayatensis
What is antigen detection used to detect?
Clostridium difficile toxin
Some viruses, e.g. adenovirus, rotavirus
How are NAATs used for diagnosis?
Can be performed directly on faeces specimen
Can be multiplex to detect several common causes
PCR can be used to look for toxin genes
What is Campylobacter?
Curved gram negative bacterium
What are the most common Campylobacter species in the UK?
C.jejuni
C.coli
What are characteristics of campylobacter?
Relatively thermotolerant
Microaerophilic (need 5% CO2)
What is the reservoir for campylobater?
Poultry (C.jejuni)
50-90% of poultry are contaminated
What is the mode of transmission of campylobacter?
Consumption of contaminated raw or undercooked poultry
What is E.coli?
Gram negative rod bacillus
What are normal flora of the large bowel?
Anaerobes, eg. Bacteroides sp.
Enterobacterales (coliforms) eg. E.coli
Enterococci
How can strains of E.coli be differentiated?
By antigenic profile or other properties such as ability to cause disease, different biochemical properties, molecular subtype or WGS
How are strains of E.coli differentiated by antigenic profile?
Somatic ‘O’ antigen
Flagellar ‘H’ antigen
Capsular ‘K’ antigen
What are commensal E.coli?
Strains of E.coli that live commensal in the GI tract
Do not cause disease in this location
Part of normal flora
Do not produce toxins or have any other disease producing mechanism
What are pathogenic E.coli?
If an ETEC, EPEC, EIEC or EHEC strain is introduced into the GI tract, then disease will result, i.e. diarrhoea or dysentery
How many strains of E.coli cause disease?
6 different strains:
* Shiga toxin-producing E. coli (STEC): This pathotype is also called enterohemorrhagic E. coli (EHEC) and verocytotoxin-producing E. coli (VTEC)
* Enterotoxigenic E. coli (ETEC): This commonly known causes of travellers’ diarrhoea
* Enteroaggregative E. coli (EAEC)
* Enteroinvasive E. coli (EIEC)
* Enteropathogenic E. coli (EPEC)
* Diffusely adherent E. coli (DAEC)
Describe STEC
Acts as commensal in many animals but pathogenic in man
Found in cows and other farm animals
Faeco-oral route
Infection occurs upon consumption of contaminated food - meat, vegetables, fruit juices
How can strains of E.coli be differentiated by biochemical profile?
E.coli can ferment wide range of sugars, most strains ferment sorbitol
VTEC strain cannot ferment sorbitol so this inability can be used to spot this strain in the lab
What is the mechanism of action of STEC?
- Shiga toxins have a monomeric enzymatically active A subunit non-covalently linked to a pentameric B subunit
- B subunit binds to glycosphingolipid globotriaosylceramide (Gb3) in lipid rafts on surface of target cells
- Shiga toxin and it receptor are endocytosed and toxin is activated through cleavage of A subunit into 2 fragments (A1 & A2) by protease furin
- Disulfide bonds keep the 2 fragments together in the endosome
- Shiga toxin avoids the lysosomal pathway and is directed to ER where the disulfide bond is reduced
- A1 subunit translocates to cytoplasm where it exerts its cytotoxic effects
- Processed A1 fragment cleaves one adenine residue from 28S RNA of the 60S ribosomal subunit, inhibiting protein synthesis and triggering ribotoxic and ER stress responses
- Shiga toxin also activates multiple stress signalling and apoptotic pathways, and is responsible for prod of inflammatory cytokines by target cells
What is the mechanism of action of ETEC?
- ETEC becomes anchored to enterocytes of small bowel via colonisation factors (CFs) and an adhesin found at the tip of the flagella (EtpA)
- Tighter adherence facilitated by outer membrane proteins Tia and TibA
- Heat-labile enterotoxin (LT) and heat-stable enterotoxin (ST) are secreted and cause diarrhoea through cyclic AMP (cAMP) and cyclic GMP (cGMP)-mediated activation of cystic fibrosis transmembrane conductance regulator (CFTR)
How do STs work?
Small toxins that can be further classified into STa and STb
- STa binds to guanylyl cyclase receptors on the brush border of the intestine and stimulates their activity (increase in cGMP)
- This causes impaired Na+ absorption and activation of CFTR
How do LTs work?
AB5 toxin secreted from pole of bacterial cell
Associates with lipopolysaccharide on the surface, where it may act as an adhesin, facilitating attachment to host cells
- B subunit of LT interacts with monosialoganglioside GM1 on host cells
- Toxin internalised at lipid rafts and trafficked to cytosol through ER
- The A subunit ADP-ribosylates the stimulatory G protein alpha subunit which activates adenylyl cyclase
- Increase in levels of cAMP, activating PKA, which activates CFTR
What can salmonella cause?
Typhoid (enteric fever)
Food-poisoning (non-typhoidal)
What types of salmonella cause typhoid?
S.typhi and S.paratyphi A, B and C
Describe typhoid
GI tract infection with systemic involvement
Diarrhoea is not a prominent symptom
Bacteria can be isolated from faeces but also from blood
Low inoculum
Source = food
What is meant by inoculum?
The required concentration of microorganisms for a standard test
Describe non-typhoidal salmonella
Common cause of infectious diarrhoea
Large inoculum needed
Usually only diarrhoea, abdo pain, cramps
Rarely fatal
Source = food; meat, eggs, reptiles
Rarely needs antibiotics
How is salmonella identified?
By culture
Serological profile
Common antigenic profiles
How can culture be used to identify salmonella?
Non-lactose fermenting GNR
May have specific appearance on selective and differential medium
Other biochemical properties
How can serological profile be used to identify salmonella?
O and H antigens
Kauffmann-White scheme (classification system allowing differentiation of serological varieties of Salmonella) - works by determining which surface antigens are produced by the bacterium
How are common antigenic profiles used to identify salmonella?
Salmonella enteritis = O9 Hg
Salmonella typhimurium = O4 Hi
Salmonella typhi = O9 Hd Vi+
These are serovars
What is enteric fever?
Usually an imported infection (e.g. returning traveller)
Human source and reservoir
Incubation 7-14 days
Invasion of lymphoid tissue of gut - intracellular, systemic spread
Inflammation of Peyer’s patches - may lead to perforation
What are symptoms of enteric fever?
Malaise
Headache
Fever
Constipation
Cough
How is enteric fever diagnosed?
Blood cultures and stool samples
How is enteric fever treated?
Needs antibiotic treatment, some patients become long-term carriers
Oral vaccine
What is Shigella?
Non-lactose fermenting GNR
What species of shigella are present in the UK?
Shigella sonnei
Shigella flexneri
What additional shigella species are present overseas?
Shigella boydi
Shigella dystenteriae (severe disease more likely)
How is Shigella transmitted?
Food and water but also close contact
Low inoculum needed
What happens when infected with shigella?
Invasion of epithelia cells of large bowel plus toxin in S.dystenteriae
How are bacterial infectious diarrhoeal illnesses treated if confined to GI tract?
Fluid and electrolytes
Antibiotics - quinolones, azithromycin
How is extra-enteric disease treated?
Systemic antibiotics (IV or oral) - usually quinolones, azithromycin, ceftriaxone
If typhoid or paratyphoid then requires treatment
What is clostridium difficile?
Gram positive anaerobic rod
Obligate anaerobe
Spore forming
Coloniser of human gut in up to 5% of adults
What are the risk factors for C.difficile infection and disease?
Antibiotic use
Hospitalisation and length of stay
Age
PPI (proton pump inhibitor)
Hypoalbuminemia
How does C.difficile act?
Disrupts microbial ecosystem within gut
Antibiotics provide competitive advantage to spore forming anaerobes over non-spore forming anaerobes
Allows C.difficile colonisation and growth, increasing numbers in the gut
What are the 3 known toxins of C.difficile?
Cytotoxin A and B
Binary toxin
What are the cytopathic characteristics?
Patchy necrosis with neutrophil infiltration
Epithelial ulcers
Pseudomembranes - leucocytes, fibrin, mucus, cell debris
How is C.diff treated?
Removing offending antibiotic
Fidaxomicin
Metronidazole
Vancomycin
(All oral)
Surgery - partial or total colectomy
How is severe C.diff treated?
Vancomycin oral and metronidazole IV
How is C.diff diagnosed?
Raised WBC in blood
Faeces specimen
2 phase test - glutamate dehydrogenase (if positive then Toxin ELISA for toxin A and B)
PCR for toxin genes
Toxigenic culture (gold standard)
What causes cholera?
Vibrio cholerae O1
Faecal contamination of water and food
What does Vibrio cholerae produce?
Heat labile enterotoxin
How is cholera treated?
Fluid replacement
Oral vaccine available
What media is required for isolation of cholera?
Thiosulfate citrate bile salts sucrose (TCBS)
What are some other bacteria that can cause infectious diarrhoea?
Vibrio parahaemolyticus
– Halophilic vibrio - seafood
Aeromonas sp
– Several species, may cause etraintestinal infection
Plesiomonas shigelloides
– Antigenically similar to shigella
Yersinia enterocolitica, Yersinia pseudotuberculosis
– Associated with pork, rare in UK but common in Europe
Listeria monocytogenes
– Probably commoner than realised
What is norovirus?
Small round structured virus
Calcivirus - small, non-enveloped (not killed by alcohol gel), RNA virus, 5 genogroups (I, II and IV found in humans)
What are clinical features of norovirus?
Vomiting often projectile
Diarrhoea
Nausea
Abdo cramps
Headache
Myalgia
Chills
Fever
How is norovirus transmitted?
Faecal-oral
Vomiting - aerosol dissemination
Contaminated environment leading to airborne/oral/mucous membrane spread
What is rotavirus?
Extremely rare infection
Was once the most common cause of infantile gastroenteritis in UK
Continues to be a leading cause of infection and deaths in developing countries without a vaccine
What is adenovirus?
DNA virus
Common cause of gastroenteritis in infants worldwide
Self-limiting but can cause fluid loss and dehydration
Diagnosed by NAAT or EM
What is crytosporidium?
Protozoan parasite
What causes cryptosporidiosis?
Cryptosporidium hominis or C.parvum
Where is cryptosporidiosis most commonly seen?
In children between 1-5 years
People with weak immune systems may be more seriously affected
What are the symptoms of cryptosporidium?
Most common symptom is mild to severe watery diarrhoea that can be prolonged
No good treatments available
What have outbreaks of cryptosporiosis been linked to?
Drinking or swimming in contaminated water (they are resistant to chlorine) and contact with infected lambs and calves during visits to open farms
How is cryptosporidiosis diagnosed?
NAAT or microscopy
Describe giardiasis
Children infected more than adults
Worldwide distribution but more common in warmer climates
Causes diarrhoea, bloating, flatulence
May be asymptomatic
Can lead to malabsorption
Treatable
How is giardiasis diagnosed?
Microscopy
NAATs
Serology
What type of virus is Hep A?
RNA
How is Hep A spread?
Faecal-oral route
What type of virus is Hep E?
Single stranded RNA
