viral gastroenteritis

Question 1

Signs/sx of viral gastroenteritis

Answer 1

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

Question 2

1. List/Name viruses that can cause gastroenteritis.

Answer 2

Calciviruses (norovirus, saporovirus), rotavirus, enteric adenoviruses, astroviruses

Question 3

viral gastroenteritis pathophys

Answer 3

1. 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

Question 4

When is a specific viral diagnosis useful

Answer 4

a. Outbreak situations for epidemiologic purposes. b. Immune compromised hosts. c. Severe disease

Question 5

2. Explain how diagnosis of gastroenteritis viruses is made even though most of these viruses cannot be grown in cell culture.

Answer 5

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.

Question 6

viral gastroenteritis treatment

Answer 6

rehydration- oral Na, K, bicarb and glucose or IV fluids if severe

Question 7

Viral gastroenteritis prevention

Answer 7

hygiene, sanitation, isolation. Vaccine for rotavirus and norovirus in development

Question 8

types of caliciviruses

Answer 8

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

Question 9

Principal cause of norovirus outbreaks in US currently

Answer 9

GII.4 Sydney norovirus serotype- first detected in 2012 in Australia

Question 10

Norovirus structure

Answer 10

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.

Question 11

norovirus clinical characteristics

Answer 11

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

Question 12

norovirus epidemiology

Answer 12

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.

Question 13

norovirus infectious dose and shedding

Answer 13

•Infectious dose: 10-100 viruses. Shedding occurs for 4 days to 8 weeks and is often asymptomatic. Stool viral load: 10 million/mL

Question 14

Norovirus immunity

Answer 14

Immunity for 6 months after infection. Antibody confers short term protection but virus strain diversity and antigenic shift play role.

Question 15

Who is innately resistant to norovirus

Answer 15

Blood group antigens. FUT2 gene required for virions to bind intestinal cells. FUT2 -/- are resistant

Question 16

norovirus diagnosis and treatment

Answer 16

Antigen tests are available but RT-PCR is more sensitive and multiplex PCR panels include norovirus. Treatment is rehydration and electrolyte corrections

Question 17

Norovirus potential drug targets and vaccine prospects

Answer 17

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

Question 18

rotavirus structure

Answer 18

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

Question 19

list the viral proteins and functions (if any) for each layer of the rotavirus protein shells

Answer 19

outer capsid: VP7 with VP4 spikes. Induce neutralizing antibody and provide acid stability. Inner capsid: VP6, major rotavirus antigen. Innermost core: VP2

Question 20

What determines the serotpye of rotavirus

Answer 20

•depend on antigenicity of surface proteins VP7 and VP4 in outer capsid layer

Question 21

classification of rotavirus

Answer 21

12 major genotypes (1-4 and 9 infect humans). Groups A-G based on inner capsid layer. Group A is most important human group.

Question 22

rotavirus reassortment

Answer 22

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

Question 23

rotavirus replication

Answer 23

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.

Question 24

rotavirus activation

Answer 24

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

Question 25

rotavirus pathogenesis

Answer 25

small intestine- replicates in villus epthelial cells, mononuclear inflammation, villus shortening/stunting. Diarrhea may be caused by decreased absorption by villi or NSP4 enterotoxin.

Question 26

Describe actions of the rotavirus enterotoxin

Answer 26

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

Question 27

rotavirus clinical manifestations

Answer 27

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.

Question 28

rotavirus incubation period and viral shedding

Answer 28

incubation: 1-3 days. Peak viral shedding on day 3, can be prolonged (>3 weeks)

Question 29

rotavirus transmission

Answer 29

fecal oral, remains infective for long periods on surfaces. Water, food, respiratory transmission less frequent. Malnourished, elderly and immunocompromised are high risk

Question 30

rotavirus diagnosis and treatment

Answer 30

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

Question 31

Rotavirus immunity

Answer 31

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

Question 32

rotavirus vaccines

Answer 32

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

Question 33

Enteric adenoviruses structure

Answer 33

Non-enveloped, icosahedral dsDNA viruses

Question 34

Enteric adenovirus clinical manifestations

Answer 34

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.

Question 35

enteric adenovirus epidemiology

Answer 35

peak incidence 2 years. No seasonality. Incubation 3-10 days. Fecal oral spread

Question 36

enteric adenovirus diagnosis and treatment

Answer 36

diagnosis: electron microscopy, antigen immunoassays, PCR, difficult to grow in culture. Treatment: rehydration, no vaccine available

Question 37

astroviruses structures

Answer 37

Small non-enveloped viruses with single stranded, plus sense RNA genomes, star shaped capsomers.

Question 38

astroviruses virology

Answer 38

Can be grown in viral culture using human intestinal epithelial cell. Trypsin required to activate infectivity. 7 serotypes.

Question 39

Astroviruses epidemiology

Answer 39

•Outbreaks in daycares, nursing homes, school cafeterias, nursing homes. Person to person spread and foodborne. Excreted for prolonged periods in immunocompromised.