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  • This lecture is about the causative organisms of gastroenteritis

Aims

Gastroenteritis

  • Epidemiology
    • Gastroenteritis is one of the leading causes of death by infectious disease
      • 1/3 of children that die every year die form diarrhoea diseases
      • Most childhood deaths are in developing countries
    • Contributed to by the background of malnutrition
    • About 1 case/person/year in Australia (most is viral)
  • Symptoms: vomiting, diarrhoea, malaise, fever
  • Aetiology: viruses, bacteria and parasites
    • Replicate in the gut, cause associated sequelae

Characteristics of common human enteric viruses associated with acute gastroenteritis

  • Most of these viral diseases last about 1 week, and have similar symptoms
  • Norovirus causes nearly all of the deaths due to gastroenteritis in Australia - due to dehydration, mainly in the elderly

Agents of gastroenteritis

  • Parasites are a small contributor
  • Bacteria = 1/3
  • Viruses are the biggest player

Genome structures and morphology

  • No envelope
  • Only DNA virus we're concerned with is adenovirus (80-100 nm wide)
    • 12 corners of the icosahedron has a protein that sticks out (can identify it by this)
  • RNA viruses
    • all encode around 8-10 proteins/genes
    • all naked, no envelope
    • rotavirus - double stranded segmented (11 segments) RNA virus - will undergo reassortment (similar to influenza)

Properties of naked capsid viruses

  • Induce more of an immune response than envelope viruses because they don't have host membrane to protect them

The gut

  • The largest mucosal surface and largest lymphoid organ
    • Fertile ground for viral replication
  • Natural flora can protect to an extent, increases in number further down the tract
    • Thus, gastroenteritis is more common in infants because the gut hasn’t developed natural flora yet

Faeces

  • Waste/excrement from the digestive tract
    • Made up of water, food residue, bacteria, and secretions from the liver and intestine
  • Diarrhoea – frequent passage of watery bowel movements
  • Causes death most commonly by dehydration

Viruses

  • Gastroenteritis is caused by parasites (2.4%), bacteria (27.1%) and viruses (70.5%)
    • Of viruses, there are 4 main agents: norovirus(47%), astrovirus(5%), adenovirus(9%), rotavirus(39%)
  • Morphology of viruses
    • DNAviruses
      • Enveloped – pox, herpes, hepatitis B
      • Naked capsid viruses – adenovirus, parvovirus-single strand
    • RNAviruses
      • +ve RNA strand: naked (norovirus, sapovirus, astrovirus), enveloped (rubella, SARS)
      • -ve RNA strand: enveloped (rabies, influenza)
      • +ve and –ve RNA: double capsid (rotavirus)
      • +ve RNA via DNA: enveloped (retrovirus: HIV)

Naked capsid viruses

  • Environmentally stable, resistant to:
    • Acid, temperature, proteases, detergents, dessication
  • Consequences of this:
    • Easily spread
    • Retains infectivity after drying
    • Resistant to detergents, and sewage treatment
    • Survives in the gut
    • Induces an immune response

Norovirus

  • Non-enveloped ssRNA virus
  • 27-35 nm in size
  • Infectious dose of 10-100 virus particles
  • Limited immunity
  • 50% of outbreaks are in hospitals, then childcare and aged care
  • 6-7 nonstructural proteins involved in replication
  • Figure 1: The Norovirus 7.5 kb genome. Open reading frames are depicted by black lines and proteins by cylinders. The triangle represents the recombination breakpoint at the ORF1/2 19 bp overlap .
  • Multiple modes of transmission, mainly through poor hygiene. Also through vomit aerosols, contaminated food or water.
  • Vomiting and diarrhoea at the same time (massive dehydration)

Critical Characteristics

  • Highly contagious
  • Multiple modes of transmission
  • Stabile in the environment
  • Resistant to routine disinfection methods
  • Asymptomatic infections

Symptoms

  • Vomiting
  • Diarrhea
  • Nausea
  • Abdominal cramps
  • Headache, muscle aches
  • Fever (minority)
  • Dehydration in young and elderly victims
  • Up to 30% may be asymptomatic

Transmission

  • Tolerant to temperature change
  • Survives high levels of chlorine
  • Transmission through the fecal-oral route
  • Highly contagious
  • Hotel restaurant with 126 patrons
  • Patron vomited at table
  • 52 of 83 survey responders ill
    • 63% overall attack rate
  • Attack rates higher at closer tables
  • Consistent with airborne transmission of NoV

Foods most at risk

  • Shellfish (oysters, clams, mussels)
  • Ready to eat foods that require handling but no subsequent cooking
    • Salads
    • Peeled fruits
    • Deli-sandwiches
    • Finger foods
    • Hors d’oeuvres
    • Dips
    • Communal foods


Norovirus detection

  • Reverse transcriptase polymerase chain reaction (RT-PCR) of stool
    • Sequencing for genotype and strain ID
  • Direct & immune EM of stool samples
  • Enzyme immunosorbant assays (EIA)

Infection control strategies

  • Patients-
    • Isolate/ cohort symptomatic patients (DB4)
    • Place on contact and airborne precautions
    • Emphasis on handwashing/cleansing after patient contact or environment
    • Duck bill masks (pt’s with explosive diarrhoea or vomiting)
    • Advice to relatives
    • Terminal clean room/ ward
    • ? Stop new admissions via A&E for 24 hr
  • Hospitals may shut down admissions, to reduce transmission
  • Common sites: prisons, ships, old peoples' homes, schools (enclosed environment, institution)

Clinical symptoms of gastroenteritis

  • Norovirus particularly
  • Symptoms lasted median of 2 days, range 0-3 days
  • Common clinical manifestations: vomiting, diarrhoea and nausea
  1. Vomiting
  2. Diarrhoea
  3. Nausea
  4. Abdominal cramps
  5. Fever/chills
  6. Sore throat
  7. Joint pain
  8. Dizzy
  9. Headache
  10. Other symptoms

Outbreak settings

Gastroenteritis epidemics - Australia

1997-2010

  • 2004 - global outbreak due a Hunter-originating version of norovirus

Norovirus epidemics in Sydney

  • Number of epidemics has been increasing since the turn of the century
  • Antigenic drift between the viruses causes a loss of herd immunity and another epidemic

Norovirus evolution by antigenic drift

  • One group of viruses (out of 30) cause all these pandemics
  • Pandemic variants of NoV arose in 1995-6, 2002, 2004, 2006, 2007-8 and in 2009/10
  • A single genotype, GII.4, has been associated with all six pandemics and numerous epidemics
  • Accumulated mutations in the P2 domain of the capsid -linked to antigenic escape from host immune responses to previous infections (very much like haemagluttinin in influenza)
  • Allows the emergence of a new epidemic NoV variant - descended from a predecessor and accumulated advantageous mutation

Rotavirus (looks like a rotor)

  • Vaccine available, motivation behind vaccination is the risk of massive dehydration, particularly in children
  • Properties:
    • 80-100nm diameter
    • 3 layers of protein
    • Enclosed double-stranded RNA genome
    • Incubation period 2-3 days
  • Types: Rotovirus A and B (A is most important)
  • Symptoms:
    • Severe dehydrating diarrhoea in infants and young children, otherwise moderate dehydration
    • Fever, vomiting, diarrhoea
      • Fever and vomiting generally decrease in 24-48 hours
  • Detection
    • EIA (enzyme immunosorbent assay)
    • Latex agglutination
    • Samples are often not taken, because you get better without treatment and thus it’s not worth finding out the cause + unpleasant taking stool sample
  • Epidemiology
    • Peak at 1 year old
    • More common in winter months

Description

Pathogenesis

  1. Viral reproduction causing cell lysis reduces the number of villi and hence the absorptive function of the small intestine, and water is lost
  2. Cell lysis releases salty solution into the lumen, increasing osmotic loss of water
  3. In the large intestine, effects on microflora and population by pathogenic organisms cause gas production etc
  • Effect on enterocytes --> loss of water, death

Rotavirus: Mechanism of infection

  • Transmitted by the faecal oral route
  • nsP4 viral enterotoxin causes diarrhoea
  • Serious in infants <24 months
  • Asymptomatic in adults
  • High viral load in diarrhoea
  • Immunity depends on IgA in lumen

Clinical manifestation

Serogroup

  • EIA - detect IgA in faeces
  • Can now test like a pregnancy test - dip it in your poo when on the toilet (most people don't like giving stool samples at GP)

Age groups

  • Mainly targeted at 1 year of age

Prevalence in Sydney

Vaccine development

Two vaccines, and they work well. Even if you do get sick, the infection is much more mild

  • Active immunisation
  1. Strains of neonatal origin
  2. Tetravalent rhesus-human ressortments
  3. G1 Rhesus strains
  4. Expressing G1 – G4
  • Protective efficacy
    • 49 – 66% against gastroenteritis
    • 69 – 100% against severe infection

Adenovirus

  • Properties
    • Double-stranded DNA genome with 30 kbp
    • Bigger genome, because DNA is more stable than RNA
    • Little pokey-out bit looks for the receptor on the cell, to enter it
      • Many serotypes: 47, only 2 cause gastroenteritis (40 and 41)
    • May enter via respiratory tract or alimentary tract and cause gastroenteritis
  • Epidemiology
    • Causes diarrhoea in infants throughout the world
      • Causes 2-3% of infant diarrhoeal disease in developing world
    • 90% of symptomatic disease occurs in < 2 year olds
  • Comparison vs rotavirus:
    • Rotavirus commonly causes fever, adenovirus less commonly
    • Rotavirus has a shorter duration: 5-7days, adenovirus: 10-14days

Clinical manifestations

  • Can't distinguish any of these viruses based on clinical features - need ELISA test.
  • Causes between 3-7% of childhood gastro
    • Astrovirus also causes about 5% of childhood gastro

Astrovirus

Description

  • Properties:
    • Small round virus
    • Single stranded RNA genome
    • 7 human serotypes exist

Epidemiology

  • Common in infants and young children
    • 3rd or 4th commonest infection in children
    • More common in cooler months – survives longer outside the body in cold weather
  • Outbreaks have occurred in nosocomial, daycare facilities, military recruits, elderly
  • Immuno-deficient individuals at risk

Clinical manifestations

Treatment of gastroenteritis

  • Need a gastrolyte (not just water)

Summary of virus information

  • Epidemiology
    • common amongst children
    • norovirus affects children and adults
    • rotavirus commonest (not any more - it's norovirus)
    • astrovirus in domicillary settings
    • adenovirus similar to astrovirus in incidenc

Norovirus

  • Began in Norwalk, Ohio
  • Properties:
    • Non-enveloped ssRNA virus
    • 27-35nm in size
    • Infectious dose is 10-100 virus particles – highly contagious
    • Drifts/mutates and thus there is limited immunity
  • Highly contagious:
    • Multiple modes of transmission – vomit, diarrhoea
    • Stable in the environment and resistant to normal disinfection methods (because it is non-enveloped)
    • Can be asymptomatic
  • Symptoms – often last for 2 days, (0-3 days)
    • Vomiting
    • Diarrhoea
    • Nausea, abdominal cramps
    • Headache, muscle aches, fever
    • Dehydration
    • Up to 30% can be asymptomatic
  • Transmission
    • Methods:
      • Faecal-oral: water, food
      • Person to person
      • Eg: hotel restaurant: vomit at table, 25% 4 tables away got sick, 90% at table
    • Food at risk
      • Shellfish (oysters, clams, mussels) – filter water and concentrate virus
      • Ready to eat foods that require handling but are not cooked
      • Eg: salads, sandwiches, fruit, finger foods, dips, communal foods
    • Places at risk:
      • Cruise ships, nursing homes, childcare centres, hotels
  • Detection:
    • Reverse transcriptase polymerase chain reaction (RT-PCR)of stool
      • Thus, sequencing of genotype and strain identity
    • Direct electro-microscopy of stool samples
    • Enzyme immunosorbent assays (EIA)
  • Infection control
    • Isolation
    • Emphasis on hygiene and PPE: eg.masks
    • Education, advice to relatives
    • Terminal clean room/ward
    • Maybe stop admissions to A and E for 24 hours
  • Genome
    • 3 parts: capsid, structural protein, protease, RNA polymerase, helicase
    • 5 genogroups: groupII is the most common in human outbreaks
  • Historical outbreaks
    • US 95/96 strain(1997-2000)
    • Farmington Hills virus-2002
    • Hunter outbreak–2004
    • 2006a outbreak–2006
    • 2006b outbreak–2007
    • Since then, a network has been set up throughout Australia to track norovirus
  • Treatment
    • Disease is self-limiting
    • In children, can lead to life-threatening dehydration
    • Intervention targets hydration and nutrition

Virus trends

  • Gastroenteritis common among children
    • Norovirus affects children and adults
    • Astrovirus is common in domicillary settings
  • Management:
    • Oral rehydration
    • Prevention and treatment of dehydration and nutritional compromise
    • Anti-dysmotility drugs



Bacterial non-colonisers

  • If you get sick in under 12 hours from eating something, then it's a non-coloniser (due to toxin, doesn't rely on bacterial replication)
  • DON'T GIVE ANTIBIOTICS - treatment is supportive
  • Produce toxins
  • Examples:
    • Staphylococcus aureus
    • Clostridium perfringens
    • Bacillus cereus
  • Illness is a result of exposure to contaminated foods
    • Short incubation time (1-6hours)
  • Symptoms: vomiting, diarrhoea
  • Treatment is generally supportive

Bacterial colonisers

Takes at least 12 hours before it colonises and causes diarrhoea

  • Examples:
    • Salmonella, Shigella, Campylobacter, Yersina, Escherichia coli, Clostridium difficile
  • Laboratory analysis:
  • Microscopy looking at: white cells, red cells, food particles, fat globules, cysts, ova and parasites
    • Culture for bacterial pathogen

Laboratory analysis

  • White blood cells in faeces --> more indicative of bacterial infection rather than viral
  • Look for cysts and ova for parasites


Salmonella

  • Properties:
    • Gram negative bacilli with flagella (similar to E. coli)
    • Adaptable to different environments – found in contaminated foods(milk and meat)
    • Serotyping is important
  • Enteric fever or typhgoid often acquired overseas
  • Non-typhoid salmonella
    • Most common form of salmonellosis
    • Incubation period of 6-48 hours
    • Symptoms – last 2-7days
      • Nausea, vomiting, diarrhoea
  • Treatment
    • Antibiotics if systemic infection
  • Supportive care/hydration

Shigella

  • Epidemiology
    • Highly contagious but does not survive well in the environment
    • Increased risk: hygiene, sexual activity, closed populations
    • More common in developing countries
  • Transmission
    • Faecal-oral
    • Food and water
  • Species:
    • Shigella sonnei, flexneri, dysenteriae
  • Properties:
    • Low infectious dose–resistant to stomach acid
    • Incubation period of 1-3 days
    • Can invade cells of the colon if there is non-motility
      • Thus can lead to an inflammatory response and blood and mucus in the stools
  • Treatment:
    • Supportive care
    • Treatment is recommended for all cases since it is a public health issue – causes infection with low inoculum
    • Antibiotics: norfloxacin, ciprofloxin, ampicillin, co-trimoxazole

Campylobacter

  • Commonest bacterial pathogen
    • Egs:Campylobacter jejuni, coli
  • Epidemiology
    • Warm weather in temperate climates
  • Transmission
    • Faecal-oral transmission
      • Infected people can shed for several weeks
    • Poultry is a common source
  • Properties:
    • Incubation time of 1-7 days
    • Curved gram –ve bacilli,non-spore forming
    • Can invade gut mucosa
    • Toxins: enterotoxin, cytotoxin
  • Symptoms:
    • Fever
    • Leukocytosis
    • Abdominal cramp
    • Blood in the stool–duetomucosalinvasion
  • Treatment
    • Antibiotics are often unnecessary
      • Used in severe cases or in risk jobs (food handlers) – erythromycin

Bacterial trends

  • Types:
    • Common: salmonella non-typhoid, campylobacter, shigella
    • Overseas: vibrio cholerae, vibrio parahaemolyticus, salmonella typhoid
    • Nosocomial: clostridium difficile
    • Less common:E.coli, aeromonas, plesiomonas shigelloids, yersina enterocolitica
  • Treatment
    • Symptomatic unless systemic infection - then antibiotics

Parasites

Giardia Lamblia

  • Obligate anaerobic protozoa that lives in the small intestines
  • Has twos tages:
    • Trophozoite stage – causes disease
      • Binucleate with 8 flagella
      • Lives in host in this form
    • Cyst stage
      • Lives outside the host in this form
      • Can survive harsh environmental conditions
      • Transmitted faecal-oral
  • Clinical presentation:
    • Asymptomatic (carriers)
    • Intermittent diarrhoea and constipation
    • Weight loss, malaise
    • Malabsorption of fat – causes foul smelling flatulence and stools
  • Diagnosis–microscopy of stool sample, EIA, biopsy
  • Treatment–Metronidazole(Flagyl)

Cryptosporidium

  • Oocysts are infectious
    • Complex lifecycle with sexual and asexual stages
    • Zoonotic potential
  • Water transmission important, filtration is best prevention method(resistant to disinfectant)
  • Important disease for immunocompromised, developing countries
  • Lack of effective therapy,maintenance of hydration is important

External links **