viral gastroenteritis Flashcards
Signs/sx of viral gastroenteritis
acute watery diarrhea w/out mucus or blood, +/- vomiting (precedes). Dehydration in infants and older adults. Nauseau, intestinal cramping, myalgias, low grade fever, headache, malaise
- List/Name viruses that can cause gastroenteritis.
Calciviruses (norovirus, saporovirus), rotavirus, enteric adenoviruses, astroviruses
viral gastroenteritis pathophys
- Local infection of intestinal epithelial cells. 2. Malabsorption due to virus killing mature enterocytes. 3. Local villus ischemia leading to diarrhea. 4. Viral enterotoxin changing transepithelial fluid balance
When is a specific viral diagnosis useful
a. Outbreak situations for epidemiologic purposes. b. Immune compromised hosts. c. Severe disease
- Explain how diagnosis of gastroenteritis viruses is made even though most of these viruses cannot be grown in cell culture.
RT-PCR detection of viral nucleic acids in stool is most sensitivie. A multiplex PCR assay can detect many of the most common viral etiologies on a single panel.
viral gastroenteritis treatment
rehydration- oral Na, K, bicarb and glucose or IV fluids if severe
Viral gastroenteritis prevention
hygiene, sanitation, isolation. Vaccine for rotavirus and norovirus in development
types of caliciviruses
Norovirus and sapovirus are the two that can affect humans. Norovirus has 3 genera that affect humans, GI, GII and GIV. There are many serotypes of norovirus which arise by mutation or recombination
Principal cause of norovirus outbreaks in US currently
GII.4 Sydney norovirus serotype- first detected in 2012 in Australia
Norovirus structure
non-enveloped ssRNA virus with cup shaped (chalice-like) indentations. Contains a viral encoded protease that cleaves viral polyproteins, necessary for viral replication. Difficult to grow in culture.
norovirus clinical characteristics
1/3 asymptomatic but shedding virus. vomiting, watery diarrhea, nausea, cramping. Associated malaise, headaches, myalgias, low-grade fevers in some. Incubation: 15hrs to 2 days. Duration of Sx: 1-2 days
norovirus epidemiology
Common cause of outbreaks on cruise ships, hospitals and nursing homes. Fecal oral spread, foodborne (shellfish) and waterborne. Most common cause of diarrhea in older children and adults, 2nd most common in young children after rotavirus.
norovirus infectious dose and shedding
•Infectious dose: 10-100 viruses. Shedding occurs for 4 days to 8 weeks and is often asymptomatic. Stool viral load: 10 million/mL
Norovirus immunity
Immunity for 6 months after infection. Antibody confers short term protection but virus strain diversity and antigenic shift play role.
Who is innately resistant to norovirus
Blood group antigens. FUT2 gene required for virions to bind intestinal cells. FUT2 -/- are resistant
norovirus diagnosis and treatment
Antigen tests are available but RT-PCR is more sensitive and multiplex PCR panels include norovirus. Treatment is rehydration and electrolyte corrections
Norovirus potential drug targets and vaccine prospects
Potential drug target: viral-encoded protease is necessary for cleavage of viral polyprotein. Vaccine prospects: recombinant calicivirus proteins expressed in insect cells, live attenuated virus make by mutation of viral genome. MULTIPLE SEROTYPES WOULD HAVE TO BE IN THE VACCINE
rotavirus structure
11 genome segments of double stranded RNA (each segment encodes one viral protein). Non-enveloped. Three protein shells: outer capsid layer, inner capsid layer and inner core
list the viral proteins and functions (if any) for each layer of the rotavirus protein shells
outer capsid: VP7 with VP4 spikes. Induce neutralizing antibody and provide acid stability. Inner capsid: VP6, major rotavirus antigen. Innermost core: VP2
What determines the serotpye of rotavirus
•depend on antigenicity of surface proteins VP7 and VP4 in outer capsid layer
classification of rotavirus
12 major genotypes (1-4 and 9 infect humans). Groups A-G based on inner capsid layer. Group A is most important human group.
rotavirus reassortment
Reassortment of genome segments occurs whenever two different rotaviruses infect the same cell. Reassortment allows introduction of segments from animal rotavirus into human rotavirus, causing epidemics
rotavirus replication
Rotavirus virions assemble at RER, where inner cores are enveloped in a transient envelope, which loses its lipid and becomes the outer protein shell of the virion in the lumen of the RER.
rotavirus activation
Virions are not infectious unless activated by treatment with trypsin. Trypsin is available in the gut. It cleaves an outer capsid protein and aids in virus uncoating
rotavirus pathogenesis
small intestine- replicates in villus epthelial cells, mononuclear inflammation, villus shortening/stunting. Diarrhea may be caused by decreased absorption by villi or NSP4 enterotoxin.
Describe actions of the rotavirus enterotoxin
NSP4 enterotoxin- destabilizes membranes leading to cell death. Mobilizes intracellular Ca activating signal transduction pathway to transport from ER. Cl secretion with water following. Possible activation of enteric nervous system
rotavirus clinical manifestations
up to 50% are asymptomatic. Abrupt onset fever, vomiting followed by diarrhea. Stools are explosive, watery, nonbloody. Dehydration in children. Sx last 4-8 days, self limited.
rotavirus incubation period and viral shedding
incubation: 1-3 days. Peak viral shedding on day 3, can be prolonged (>3 weeks)
rotavirus transmission
fecal oral, remains infective for long periods on surfaces. Water, food, respiratory transmission less frequent. Malnourished, elderly and immunocompromised are high risk
rotavirus diagnosis and treatment
Antigen detection via ELISA of stool (rotazyme), RT-PCR, or multiplex PCR panels. Treatment: rehydration and electrolyte correction. Probiotics may decrease frequency and duration of diarrhea
Rotavirus immunity
Serum and intestinal IgM, IgG and IgA. Cellular immune response. Repeated infections may occur but are generally milder. Symptomatic infection less common in <6mo due to protective role of breast feeding. Chronic infection can occur in cellular immune deficiencies and transplant pts
rotavirus vaccines
RotaTeq (RV5): pentavalent live bovine rotavirus vaccine. Contains outer capsid proteins of 5 human RV strains made by reassortment with bovine RV. Oral, 3 doses (2,4,6months). 98% protective against severe dz. Rotarix (RV1): monovalent live human rotavirus vaccine. Cross protection against other strains. Oral, 2 doses (2, 4 months). 85% protective against severe dz
Enteric adenoviruses structure
Non-enveloped, icosahedral dsDNA viruses
Enteric adenovirus clinical manifestations
Typically associated with URI symptoms, conjunctivitis, pharyngitis, pneumonia, hemorrhagic cystitis, but serotypes 40, 41 can cause gastroenteritis. Watery diarrhea, then vomiting lasting 5-12 days (longer than most viruses). Can cause persistent severe infection in immunocompromised. reinfections can occur.
enteric adenovirus epidemiology
peak incidence 2 years. No seasonality. Incubation 3-10 days. Fecal oral spread
enteric adenovirus diagnosis and treatment
diagnosis: electron microscopy, antigen immunoassays, PCR, difficult to grow in culture. Treatment: rehydration, no vaccine available
astroviruses structures
Small non-enveloped viruses with single stranded, plus sense RNA genomes, star shaped capsomers.
astroviruses virology
Can be grown in viral culture using human intestinal epithelial cell. Trypsin required to activate infectivity. 7 serotypes.
Astroviruses epidemiology
•Outbreaks in daycares, nursing homes, school cafeterias, nursing homes. Person to person spread and foodborne. Excreted for prolonged periods in immunocompromised.
