Enteric Infections Flashcards
Gastrointestinal Natural Resistance to Infection
- We routinely cope with low-level bacterial infection in food due to natural defenses in GI tract
- Gastric acid - fat in diet may protect pathogens in transit
- Bile salts - in duodenum disrupt some cell surfaces
- Normal commensal flora
- Modify environment with metabolites
- Compete for nutrients
- Produce natural antibiotics
- Mucosal immunity
- Cell-mediated immunity
- Secretory IgA (also in breast milk)
- Motility - diarrhoea probably important in clearing pathogens
Hydration/Rehydration
- Our survival depends upon the fluid absorption capacity of the gut
- Adult gut handles 6,500 ml of fluid/day
- Food
- Saliva
- Gastric/pancreatic/biliary fluids
- Volume reduced to 1,500ml by distal ileum
- Reduced further in colon –> stool egestion of <250ml a day
- Adult gut handles 6,500 ml of fluid/day
- Diarrhoea due to:
- Secretory (chloride or calcium mediated)
- +/- Osmotic (damage to villous brush border)
- Oral rehydration therapy - oral rehydration salts (ORS)
- Rely on coupled transport of sodium and glucose into enterocytes so that water follows osmotic gradient
- Now a standard of care
Types of Enteric Infection
- Type 1: Non-inflammatory (watery diarrhoea) e.g.
- Toxin-mediated
- C.perfringens
- B.cereus
- S.aureus
- Giardia
- Cryptosporidium
- Rotavirus
- Norovirus
- ETEC
- EPEC
- Toxin-mediated
-
Type 2: Inflammatory (dysentery, faecal leukocytes, lactoferrin) e.g.
- Shigella
- VTEC
- C.difficile
- C.jejuni
- S.enteritidus
- Entamoeba
-
Type 3: Penetrating (enteric fever) e.g.
- S.typhi
- Yersinia
Standard Management
- Often uncomplicated and self-limiting
- Mainstay of treatment is supportive
- Rehydration therapy
- Little role for anti-diarrhoheal agents
- Some bacteria or parasites may require specific antimicrobial therapy
- Assessing dehydraion correctly and early important
- Infants more susceptible as:
- Higher body surface to volume ration
- Smaller fluid reservoir
- Dependent on other for fluid intake
- Signs of severe dehydration
- Apathy
- Tachycardia (bradycardia if extreme)
- Weak pulse
- Deep breathing
- Deep dunken eyes
- No tears
- Parched mouth
- Skin recoil >2 seconds
- Minimal urine output
- Infants more susceptible as:
Basic Diagnosis (Bacteria/Parasites)
- Rarely possible on clinical features alone
- Epidemiology - as part of an outbreak
- Microbial investigation
- Rarely necessary unless:
- Dehydrated
- Febrile
- Blood or pus in stool
- Part of outbreak
- Stool +/- blood culture
- Sekective indicator growth mediator
- Diagnostic yield of stool culture approximately 5%
- Microsopy of stool for:
- Ova
- Cysts
- Parasites
- Specific typing
- Rarely necessary unless:
E.Coli

- Major part of normal gut flora
- Until recently role uncertain as difficult to distinguish pathogens from commensals
- Enterotoxic E.coli (ETEC)
- Produces two main types of polypeptide toxins (similar to cholera) –> hypersecretion of fluid into lumen
- Verycytotoxic (VTEC) or Enterohaemorrhagic (EHEC)
- Produces cell killing cytotoxin (similar to shigella)
- Can ==>
- Haemmorhagic colitis
- Haemolytic uraemic syndrome (HUS)
- Enteroinvasive (EIEC)
- Enteropathogenic (EPEC)
- Enterotoxic E.coli (ETEC)
E.Coli - Epidemiology
- Transmission by:
- Faecal-oral
- Direct
- Food or water
- ETEC
- Commonest cause of bacterial diarrhoea in children in areas of poor hygeine
- Uncommon in Western Europe
- Important cause of travellers’ diarrhoea
- Reservoir = human GI tract
- VTEC
- Several types - commonest is 0157
- Now a common cause of acute renal failure in Western countries
- Reservoir = GI tract of healthy cattle
- Transmission by:
- Contaminated food/animal carcases (e.g. hamburgers)
- Unpasteurised milk
- Farms
- Paddling pools
- Rarely person to person e.g. nurseries
- Several types - commonest is 0157
E.Coli - Clinical Features
- Incubation period usueally 1-5 days (can be up to 14)
- Abrupt onset vomiting and diarrhoea
- ==> later profuse watery diarrhoea only
- Mild fever
- Little pain
- Similar presentation to viral gastroenteritis/salmonellosis
E.Coli - Haemorrhagic Colitis
- Possible complication of 0157 infection in children and adults
- Typically diarrhoea escalates to bloody with abdominal pain
- Fever usually low
- May be mistaken for acute inflammatory bowel disease
E.Coli - Haemolytic Uraemic Syndrome
- May accompany colitis as a complication of infection
- Affects 10% of children in outbreaks
- Characterised by:
- Rising urea and creatinine (AKI)
- Haemolytic anaemia
- Thrombocytopenia
- Raised BP
- Prognosis
- >50% need haemodialysis
- Only fatal in <5% - mostly elderly
- Preceeding GI illness may go unrecognised
- Shiga-toxin binds to glomerular epithelium ==> apoptosis + bind leukocytes + become thrombogenic ==> activated platelet complexes lodge in capillaries and arterioles ==> destruction of RBCs (microangiopathic haemolysis)
E.Coli - Laboratory diagnosis
- Difficult as pathogen and normal flora are the same species
- 0157:
- Phage typing
- Doesn’t ferment sorbitol
- Immunological cytotoxin detection
- PCR detection of cytotoxin gene
E.Coli - Management
- Mostly supportive
- Many E.Coli are resistant to broad spectrum antibiotics e.e.g penicillins, cephalosporins, trimethoprim
- Rx -* ciprofloxacin* 500mg BD for 3-5 days
- **! **- Avoid antibiotics in HUS as bactericidal ==> toxin release
- Antimotility drugs probably increase chance of HUS through delayed clearance of toxin
Salmonella

- Common cause of food poisoning
- Infects humans and other animals
- >2000 serotypes
- Commonest are S.enteritidis, S.typhimurium and S.virchow
-
Cause of typhoid and paratyphoid fevers
- These are exclusive human pathogens
Salmonella - Food Poisoning
- Contaminated poultry/dairy products common source
- Not usually from food handlers or person to person spread
- Reservoir - GI tract of birds, reptiles, amphibians
- Commoner in summer/hot weather
- Microbiology:
- Identified on specific media by biochemical features:
- Non-lactose fermenters
- Produce H2S
- LPS is O antigen, flagellae H antigen - defines serotypes
- Identified on specific media by biochemical features:
Salmonella - Food Poisoning - Pathogenesis
- Infection of gut epithelium
- Does not extend beyond basement membrane
- ==> Excess fluid secretion from ileum/jejenum
- If transported through cells ==> systemic infection
- Survives in macrophages
Salmonella - Food Poisoning - Clincal Features
- Incubation period 12-72 hours
- Symptoms:
- Malaise
- Nausea
- Vomiting
- Fever
- ==> Watery-brown diarrhoea follows rapidly
- Abdominal pain common but not severe
- Often resolves in several days, some cases last several weeks
- Children and elderly at risk of hypovolaemia
Salmonella - Food Poisoning - Complications
- Salmonella colitis
- Affects up to 10% ==> colic and bloody stools
- Bacteraemia
- ==> Seeding to bones/joints in sickle cell disease patients
- ==> Aneurysms
- Post-infectious reactive arthritis
- Prolonged excretion in:
- Diverticulosis
- IBD
- HIV
Salmonella - Microbiology
- Stool culture
- Blood culture if high fever or very unwell
- Selective agar to inhibit normal flora + indicator
- Indicator often lactose red ==> pink colonies due to lactose fermentation and acid production
- Typing:
- Bacteriophage
- Antibiotic panels
Salmonella - Food Poisoning - Management
- Rehydration
- Antibiotics if:
- No recovery after 48 hours
- Shock
- High risk
- Valve disease
- Prosthesis
- *Ciprofloxacin *first line (alternative is cefotaxime)
Shigellosis (Bacillary Dysentery) - Epidemiology

- Worldwide problem
- In Western countries endemic Shigellae usually cause mild illness
- Few thousand cases a year in the UK
- Tropical strains tend to be more severe and persistent
- Transmission via
- Person to person spread
- Contaminated food and water
- Reservoir = human GI tract
Shigellosis - Pathogenesis
- Few thousand cases a year in the UK
- Suptypes:
- *S.sonnei - *most common
- S.flexneri
- S.boydii
- *S.dysenteriae - *type 1 produces shiga exotoxin
- Invade gut by:
- Destroying submucosa
- Infecting enterocytes
- Spread for cell to cell
Shigellosis - Clinical Features
- Incubation period of 1-7 days
- Course:
- High fever
- High WBC
- With resolving fever ==> diarrhoea and colic
- S.sonnei and *S.boydii *are mild - rarely cause colitis
- *S.flexneri * and S.dysenteriae are more severe ==> mucus and blood in stool + marked colic
- Asymptomatic excretion for days-weeks
Shigellosis - Microbiology
- Like E.coli
- Non-lactose fermentors
- Non-motiles
- Serotype on basis of O antigens
Shigellosis - Management
- Symptomatic
- Antispasmodics
- Rehydrate
- Abx in severe cases
- Rx- *ciprofloxacin (trimethoprim/ceftriaxone *alternatively)
Campylobacter

- Commonest cause of food poisoning
- >50,000 cases per year in the UK
- Mostly sporadic - undercooked poultry, bird pecked milk
- Large food/waterborne outbreaks can occur
- Incidence higher in summer
- Person to person spread uncommon
- Animal pathogen - several species can infect humans:
- C.jejuni
- C.coli
- C.fetus
- C.lari
Campylobacter Jejuni
- Low infective dose
- Cell-wall LPS
- Produces enterotoxin and cytotoxin
Campylobacter - Clinical Features
- Incubation period 2-5 days (up to 9)
- 24 hour prodrome - fever + headache
- Symptoms:
- Watery diarrhoea - can be bloody
- Vomiting
- Significant pain - constant not colicky
- Pain with little diarrhoea can occur - similar to acute abdomen presentation
- Systemic infection rare
- Commonest antecedent infection identified in Guillain Barré Syndrome (a post-infectious peripheral neuropathy)
Campylobacter - Microbiology
- Selective media with antibiotics
- 43ºC incubation may improve selection
- Microaerophilic
- Gull wing morphology
Campylobacter - Management
- Mild cases usually self-limiting
- Severe/prolonged cases - Rx 3-4 day course of oral erythromycin
- *Ciprofloxacin *active against
Clostridium Difficile

- Commonest cause of hospital-acquired diarrhoea
- Gut commensal in 3% of healthy adults and 66% of children
- Some antibiotics disturb normal balance of microbial flora ==> rapid multiplication of C.difficile ==> toxin production ==> mucosal injury and inflammation ==> diarrhoea
Clostridium Difficile - Clincal Presentation
Clostridium Difficile - Risk Groups
- Age >65 years
- Antibiotic treatment - especially:
- Clindamycin
- Cephalosporins
- Penicillins
- GI surgery/manipulation
- Long stay in hospital/residential care
- Immunosuppression
Clostridium Difficile - Managment
- Confirm diagnosis by C.difficile toxin testing
- Stop or change antibiotics if possible
- Fluid/electrolyte replacement
- Avoid antiperistaltics
- If above not possible or unseuccessful - Rx metronidazole
- *vancomycin * second line
- Infection control
Viral Gastroenteritis

- Common pathogens:
- Rotavirus
- Adenovirus
- Norovirus
- Astrovirus
- Commonest cause of symptomatic intestinal infection in Western world
- Rarely severe or fatal in UK
- Significant cause of infant mortality in resource poor countries
Viral Gastroenteritis - Management
- All self-limiting in the normal host
- Rehydration is the key
- Prevention of spread
- Faecal-oral, person-person, food
- Antiviral therapy not used/available
Viral Gastroenteritis - Diagnosis
- Rarely possible on clinical grounds
- Epidemiology
- Stool electron microscopy - ‘catch all’
- Stool enzyme immunoassays (e.g. rotavirus)
- Molecular diagnosis
- Stool PCR
- Outbreak typing and molecular epidemiology
- None of these viruses can be grown in cell culture
Rotavirus

- Commonest cause of viral gastroenteritis in young children
- 1 million deaths/yr worldwide
- >10,000 cases/yr UK - under-reported
- Peak incidence 6-24 months, uncommon >5yrs but adult infection occurs and can be symptomatic – may cause outbreaks in elderly care homes
- Seasonal, late winter
Rotavirus - Virology
- Reovirus
- Segmented dsRNA genome
- No envelope
- Seven serogroups (A-G)
- Gp A human, others infect different animals e.g. pigs
- Genomes can reassort (like flu A) ==> possibility of new human strains
- Reservoir GI tract humans
- 1 billion viruses/ml faeces - only 10 needed for infection
Rotavirus - Clinical Features
- Incubation around 1 day
- Abrupt onset diarrohea and vomiting (D>V)
- Mild fever - short-lived
- Recovery in 48 hrs usual (diarrhoea for up to a week)
- Blood in stool can occur-investigate further
- Gross dehydration and shock
- Adults may have mild disease, transient vomiting
- Persistent diarrhoea may occur in immunosuppressed
Rotavirus Vaccine
- Original tetravalent rhesus monkey/human reassortment vaccine (Rotashield) withdrawn over concerns regarding intussusception
- New live attenuated vaccines (Rotarix and RotaTeq) highly effective against severe disease
- Protection against severe disease, not necessarily against infection
- Rotarix added to UK Childhood immunization programme in 2013 – 2 doses given at 2 months and 3 months of age
Calciviruses

- Types:
- Norovirus
- Sapovirus (SRSV)
- ssRNA, non-enveloped, does not grow in routine cell culture
- Reservoir human GI tract
- May be concentrated in bivalve molluscs
Norovirus Gastroenteritis
- Incubation 10-50 hrs
- Asymptomatic to explosive vomiting and diarrhoea
- Headache and abdominal cramps
- Lasts 24-48 hrs
- Common defined outbreak cause (50-60%)
- Closed communities/hospitals/cruise ships
- Breathe in aerosolised vomit/faeces and swallow
- Infectious dose low
Enteric Adenoviruses

- Second most common cause of infantile diarrhoea in temperate climates
- Adenoviruses cause many diseases
- Non-enveloped, dsDNA
- Virology
- Subgroups A-F - gastroenteritis agents are group F: types 40/41
- Poor growth in cell culture
- Standard clinical picture:
- Incubation period up to 10 days ==>
- Watery diarrhoea
- Mild fever
- Illness may last longer but in general (3-11 days)
Astroviruses

- Infants and elderly exhibit significant illness
- Severity lower than other agents
- Often co-infection with rotavirus/norovirus
- <5% hospitalised cases viral gastroenteritis
- Commoner in winter time
- Virology
- +ssRNA
- Non-enveloped
- 5-6 pointed star
- Several serotypes