Enteric Infections Flashcards

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1
Q

Gastrointestinal Natural Resistance to Infection

A
  • 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
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2
Q

Hydration/Rehydration

A
  • 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
  • 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
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3
Q

Types of Enteric Infection

A
  • Type 1: Non-inflammatory (watery diarrhoea) e.g.
    • Toxin-mediated
      • C.perfringens
      • B.cereus
      • S.aureus
    • Giardia
    • Cryptosporidium
    • Rotavirus
    • Norovirus
    • ETEC
    • EPEC
  • 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
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4
Q

Standard Management

A
  • 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
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5
Q

Basic Diagnosis (Bacteria/Parasites)

A
  • 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
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6
Q

E.Coli

A
  • 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)
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7
Q

E.Coli - Epidemiology

A
  • 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
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8
Q

E.Coli - Clinical Features

A
  • 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
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9
Q

E.Coli - Haemorrhagic Colitis

A
  • 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
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10
Q

E.Coli - Haemolytic Uraemic Syndrome

A
  • 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)
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11
Q

E.Coli - Laboratory diagnosis

A
  • 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
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12
Q

E.Coli - Management

A
  • 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
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13
Q

Salmonella

A
  • 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
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14
Q

Salmonella - Food Poisoning

A
  • 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
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15
Q

Salmonella - Food Poisoning - Pathogenesis

A
  • 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
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16
Q

Salmonella - Food Poisoning - Clincal Features

A
  • 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
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17
Q

Salmonella - Food Poisoning - Complications

A
  • 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
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18
Q

Salmonella - Microbiology

A
  • 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
19
Q

Salmonella - Food Poisoning - Management

A
  • Rehydration
  • Antibiotics if:
    • No recovery after 48 hours
    • Shock
    • High risk
      • Valve disease
      • Prosthesis
  • *​Ciprofloxacin *first line (alternative is cefotaxime)
20
Q

Shigellosis (Bacillary Dysentery) - Epidemiology

A
  • 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
21
Q

Shigellosis - Pathogenesis

A
  • 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
22
Q

Shigellosis - Clinical Features

A
  • 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
23
Q

Shigellosis - Microbiology

A
  • Like E.coli
    • Non-lactose fermentors
    • Non-motiles
    • Serotype on basis of O antigens
24
Q

Shigellosis - Management

A
  • Symptomatic
  • Antispasmodics
  • Rehydrate
  • Abx in severe cases
    • Rx- *ciprofloxacin (trimethoprim/ceftriaxone *alternatively)
25
Q

Campylobacter

A
  • 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
26
Q

Campylobacter Jejuni

A
  • Low infective dose
  • Cell-wall LPS
  • Produces enterotoxin and cytotoxin
27
Q

Campylobacter - Clinical Features

A
  • 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)
28
Q

Campylobacter - Microbiology

A
  • Selective media with antibiotics
  • 43ºC incubation may improve selection
  • Microaerophilic
  • Gull wing morphology
29
Q

Campylobacter - Management

A
  • Mild cases usually self-limiting
  • Severe/prolonged cases - Rx 3-4 day course of oral erythromycin
  • *Ciprofloxacin *active against
30
Q

Clostridium Difficile

A
  • 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
31
Q

Clostridium Difficile - Clincal Presentation

A
32
Q

Clostridium Difficile - Risk Groups

A
  • Age >65 years
  • Antibiotic treatment - especially:
    • Clindamycin
    • Cephalosporins
    • Penicillins
  • ​​GI surgery/manipulation
  • Long stay in hospital/residential care
  • Immunosuppression
33
Q

Clostridium Difficile - Managment

A
  • 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
34
Q

Viral Gastroenteritis

A
  • 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
35
Q

Viral Gastroenteritis - Management

A
  • All self-limiting in the normal host
  • Rehydration is the key
  • Prevention of spread
  • Faecal-oral, person-person, food
  • Antiviral therapy not used/available
36
Q

Viral Gastroenteritis - Diagnosis

A
  • 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
37
Q

Rotavirus

A
  • 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
38
Q

Rotavirus - Virology

A
  • 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
39
Q

Rotavirus - Clinical Features

A
  • 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
40
Q

Rotavirus Vaccine

A
  • 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
41
Q

Calciviruses

A
  • Types:
    • Norovirus
    • Sapovirus (SRSV)
    • ssRNA, non-enveloped, does not grow in routine cell culture
  • Reservoir human GI tract
  • May be concentrated in bivalve molluscs
42
Q

Norovirus Gastroenteritis

A
  • 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
43
Q

Enteric Adenoviruses

A
  • 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)
44
Q

Astroviruses

A
  • 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