VIRAL AGENTS CAUSING GASTROENTERITIS Dr. Osama AL Jiffri

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VIRAL AGENTS CAUSINGGASTROENTERITISDr. Osama AL
Jiffri
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Viral gastroenteritis

• Inflammation of stomach and small and large
  intestines
• Infection caused by a variety of viruses that
  results in vomiting or diarrhea (stomach flu)

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VIRAL AGENTS CAUSINGGASTROENTERITIS
Major Viruses

• Rotavirus
• Enteric adenoviruses
• Noroviruses
• a. Norwalk-like
  viruses
• b. Calicivirus
• c. Astrovirus

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Noroviruses

• Norwalk-like Caliciviruses Astroviruses
  other
• viruses
  viruses

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Viruses associated with gastroenteritis (cont)

• Other viruses (minor)
• Coronaviruses
• Parvoviruses
• Pestiviruses
• Toroviruses

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ROTAVIRUS

• Family Reoviridae
• Genus Rotavirus

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ROTAVIRUS

• First isolated in 1973 from children with
  diarrhea
• EM identification from duodenal biopsies
• Human and animal strains

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Rotavirus- EM Structure
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ROTAVIRUS

• 60-80nm in size
• Non-enveloped virus
• Double capsid
• EM appearance of a wheel with radiating spokes
• double stranded (ds) RNA in 11 segments
• (double double)

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Rotavirus
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ROTAVIRUS- ultrastructure
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STRUCTURE

• Double capsid (outer and inner capsid)
• Core with genome

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ROTAVIRUS- 3D STRUCTURE
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Viral Structural Proteins (VP)

• Outer structural proteins - VP7 and VP4
• VP7glycoprotein
• VP4protease-cleaved, P protein, viral
  hemagglutinin, and forms spikes from the
  surface
• Inner core structural proteins VP 1, 2, 3, 6
• VP6 is an important antigenic determinant

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Gene coding assignment
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• Genome is composed of 11 segments of
  double-stranded RNA,
• six
  structural
• coding for
  proteins
• five
  nonstructural

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Classification

• Groups, subgoups, serotypes based on viral capsid
  proteins
• Group A is the most common and has 2 subgroups
• 10 human serotypes based on G protein (VP 7)
• 8 P protein serotypes

• Seven serological groups have been identified
  (A-G), three of which (groups A, B, and C) infect
  humans .

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Rotavirus - Properties

• Virus is stable in the environment
• Relatively resistant to handwashing agents
• Susceptible to disinfection with 95 ethanol,
  Lysol, formalin

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Rotavirus Epidemiology

• Leading cause of severe gastroenteritis in
  children aged lt5 years worldwide
• Millions are affected
• 600,000-850,000 deaths/year
• A major cause of diarrhea-associated
  hospitalizations
• Seroprevalence studies show that antibody is
  present in most by age 3y.

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Estimated Global Distribution of The 800,000
Annual Deaths Caused By Rotavirus Diarrhea
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Epidemiology

• Age- 4mo - 2 yearsProtection of younger infants
  through transplacental antibody transfer
• Asymptomatic infections are common, especially in
  adults
• Nosocomial infections
• Outbreaks

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Epidemiology (contd.)

• Seasonality
• Winter months (Nov. through May in US)
• Gradual spread W to E
• Year-round in the tropics
• Incubation period - thought to be lt4 days

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Epidemiology (transmission)

• Mainly person to person via fecal-oral route
• Fomites
• Food and water-borne spread is possible
• Spread via respiratory route is speculated

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EPIDEMIOLOGYDifferences in Groups

• Group A infections are most common
• Group B has been associated with outbreaks in
  adults in China
• Group C is responsible for sporadic cases of
  diarrhea in infants around the world

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Clinical Features

• Incubation period - thought to be lt4 days
• Fever- can be high grade (gt102?F in 30)
• Vomiting, nausea precede diarrhea
• Diarrhea
• - usually watery (no blood or leukocytes)
• - lasts 3-9 days
• Dehydration is the main contributor to mortality

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• Recovery is usually complete.
• However, severe diarrhea without fluid and
  electrolyte
• replacement may result in dehydration and
  death .

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Diagnosis

• Antigen detection in stool by ELISA, Latex
  Agglutination (for Group A rotavirus)
• EM- non-Group A viruses also
• Culture- Group A rotaviruses can be cultured in
  monkey kidney cells
• Serology for epidemiologic studies

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Treatment and Prevention

• Treatment-
• Supportive - oral, IV rehydration
• Prevention-
• Handwashing and disinfection of surfaces

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Vaccine (old)

• Live tetravalent rhesus-human reassortant vaccine
  (Rotashield)
• Licensed for use in August 1998
• Removed from the market in October 1999 due to
  risk of intussusception
• Cases were seen 3-20 days after vaccination
• Approx. 15 cases/1.5 million doses

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Vaccine (New)

• New licensed vaccine ( RotaTeq)
• No elevated risk of intussusception
• In U.S.A. recommendation made to routinely
  vaccinate all children at 2,4,6 months
• Considered for routine immunization in many
  countries

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GASTROENTERITIS DUE TO ENTERIC ADENOVIRUS
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ADENOVIRUS

• A nonenveloped double-stranded DNA virus
• First isolated in the 1950s in adenoid tissue
• Gastroenteritis, upper and lower respiratory
  tract infection, ocular infections

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GASTROENTERITIS DUE TO ADENOVIRUS

• Types 40, 41
• Belong to serogroup F
• Some cases due to types 31, 3, 7

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Clinical features of Enteric Adenovirus
gastroenteritis

• Age lt4 years
• Incubation period 3 -10 days
• Diarrhea lasts for 10 -14 days

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Laboratory Diagnosis

• Isolation standard cell cultures of human
  neonatal kidney cells
• ELISA for rapid detection is available
• Complement fixation for antibody level

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HUMAN CALICIVIRUSES
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HUMAN CALICIVIRUSES(HuCV)

• Belong to Family Caliciviridae
• Non-enveloped RNA viruses
• with ss RNA
• 27-35 nm in diameter
• Contain a single capsid protein

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HUMAN CALICIVIRUSES

• Genomic analysis divides it into 4 groups
• Human caliciviruses belong to 2 genera

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CLASSIFICATION OF HuCV

• NLV (Norovirus)
• Norwalk virus
• Hawaii virus
• Snow Mountain virus
• Montgomery county virus
• Taunton (England)

• SLV (Sapovirus)
• Sapporo virus
• Manchester virus
• Houston/86
• London/92

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Morphology of HuCV- typical

• Typical morphology
• EM appearance of Star of David
• E.g.- Sapporo-like viruses

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HUMAN CALICIVIRUSES - SLV
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Morphology of HuCV- atypical

• Atypical morphology
• Smooth surface
• Small Round Structured viruses
• E.g.- Norwalk-like viruses

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Diagnosis- Human Caliciviruses

• Specimen- stool , vomitus, environmental swabs,
  not yet on foods
• Immune EM
• RT-PCR in state public health labs.
• Serology for epidemiologic purposes

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SRSV- NORWALK VIRUS
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CLINICAL FEATURES

• Epidemic in Adults and Children
• Usual incubation Period is lt24-48 hours
• (ranges from 12hrs. to 4 days)
• Short duration of illness lt3 days
• Nausea, vomiting, fever, headache
• Abdominal cramping
• Watery diarrhea

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Epidemiology-Noroviruses

• Worldwide distribution
• gt23 million cases/year in the U.S.
• Outbreaks of foodborne, waterborne and shellfish
• Most people have had infections by age 4 years
  (by seroprevalence studies)

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Spread of Norwalk virus

1. Person-to-person Fecal-oral spread
   (stool/vomitus)
2. Fecal contamination of food or water
3. Spread through fomites?

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Epidemiology-Noroviruses

• Asymptomatic infections- seroconversion but
  asymptomatic shedding of virus
• Low infective dose
• Viral excretion during recovery
• (up to 2 weeks)
• Ability to survive in water chlorination at
• routine levels

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Epidemiology of Outbreaks

• Cruise ships, schools, nursing homes, etc.
• Can involve infants and school-age children
• Source usually is contaminated food and water
  (seafood-oyster and shellfish etc.)

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HUMAN ASTROVIRUS
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ASTROVIRUS

• Belong to family Astroviridae
• 8 human serotypes are known
• Described in relation to an outbreak of
  gastroenteritis in 1975
• Detected by EM
• Immunologically distinct from Human Caliciviruses

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ASTROVIRUS- structure

• Small ss RNA virus
• Non-enveloped
• 27-32nm in size
• Round with an unbroken, smooth surface
• EM appearance of a 5 or 6 pointed star within
  smooth edge
• Contain 3 structural proteins

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ASTROVIRUS- EM STRUCTURE
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ASTROVIRUS - Epidemiology

• Worldwide
• Mainly in children lt7 years of age.
• Transmission person-to-person via
• fecal-oral route
• Outbreaks due to fecal contamination of
• sea-food or water

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ASTROVIRUS - Clinical Features

• Infants and children are most often affected
• Short incubation period 1-4 days
• Nausea, vomiting, abdominal cramping and watery
  diarrhea
• Symptoms-fever, malaise, headache

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ASTROVIRUS - Diagnosis

• EM (virus shed in stool in great numbers)
• EIA
• RT-PCR

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END of Lecture