Viral gastroenteritis

Question 1

Signs and symptoms of viral gastroenteritis

Answer 1

Acute onset watery diarrhea (no mucus or blood) +/- vomiting

Short incubation period

Short duration

Highly transmissible

Question 2

Acute gastroenteritis in the US compared to world

Answer 2

US:
2nd only to common cold in frequency
1-2 episodes/year

Worldwide:
6-7 episodes/year
Lots of deaths

Question 3

Pathophysiology of viral gastroenteritis

Answer 3

Local infection of intestinal epithelial cells

Malabsorption due to virus killing mature enterocytes

Local villus ischemia leading to diarrhea

Viral enterotoxin changing the transepithelial fluid balance

Question 4

How do diagnose viral gastroenteritis

Answer 4

Usually clinical

PCR (mutiplex Stool real time PCR)

Question 5

Treatment for viral gastroenteritis

Answer 5

Oral rehydration

Question 6

Prevention of viral gastroenteritis

Answer 6

Hygiene: handwashing, food preparation

Sanitation: toilets, water supply, diaper changing

Environmental cleaning

Isolation of patients

Vaccines: rotavirus available, norovirus in development

Question 7

Caliciviruses: Phylogeny

Answer 7

Sapovirus (humans)
Norovirus

Many human serotypes:
GII.4 Sydney: first detected 2012 in Australia
Principal cause of outbreaks in US

Variants arise by mutation or recombination

Question 8

Norovirus structure

Answer 8

Small round ssRNA virus, 27nm in diameter, with cup shaped indentations

Naked, non-enveloped

Viral-encoded protease cleaves viral polyproteins:

Difficult to grow in culture

Question 9

Symptoms of norovirus

Answer 9

1/3 asymptomatic but shedding virus
Vomiting, watery diarrhea, nausea, cramping
Malaise, headache, myalgia, low-grade fever
Occasionally dehydration

Question 10

Spread of norovirus

Answer 10

Person-to-person (fecal-oral spread)
Contaminated surfaces
Foodborne (esp shellfish)
Waterborne

Shedding after symptoms resolve

Question 11

Incubation and duration of norovirus infection

Answer 11

FAST!

Incubation: 15 hrs to 2 days
Duration of symptoms: 1-2 days

Question 12

Epidemiology of norovirus

Answer 12

“Cruiseship virus”

Has replaced rotavirus as #1 in areas where rotavirus vaccine in use

Most common cause of diarrheal outbreaks in older children and adults

Question 13

Rotavirus

Answer 13

Huge problem in developing world

Vaccine avaialble

Question 14

Rotavirus structure

Answer 14

11 double stranded RNA genome segments

Each segment encodes one viral protein (VP)

Non-enveloped, but three protein shells

Outer capsid layer: acid stability
Composed of VP7 with VP4 spikes: induce neutralizing antibody

Inner capsid layer
Contains VP6: major rotavirus group antigen

Innermost core: VP2

Question 15

Reassortment

Answer 15

Reassortment allows introduction of segments from animal

rotavirus into human rotavirus, causing epidemics

Question 16

Rotavirus Pathogenesis

Answer 16

Affects small intestine

Replicates in villus epithelial cells

Mononuclear inflammation

Villus shortening, stunting

Mechanism causing diarrhea is unclear
? Decreased absorptive properties of denuded villi
? NSP4 enterotoxin

High viral titers shed in stool (>10¹¹ viral particles/mL)

Question 17

Rotavirus Enterotoxin: NSP4

Answer 17

Maybe neurotoxin?

Causes diarrhea in animal studies

Question 18

Clinical manifestations of rotavirus

Answer 18

Up to 50% infections are asymptomatic

Symptomatic infection: abrupt onset fever and vomiting, followed by diarrhea

Stools are explosive, watery, nonbloody

Frequently leads to dehydration in children

Question 19

Incubation and Duration of rotavirus

Answer 19

Symptoms last 4-8 days, self-limited

Incubation period: 1-3 days

Peak viral shedding on day 3, can be prolonged (> 3 weeks)

Question 20

Rotavirus: Burden of Disease and epidemiology

Answer 20

Rotavirus is the single most important cause of severe infantile gastroenteritis worldwide

Before rotavirus vaccines in US:
Up to 180,000 hospitalization/yr
20-40 deaths/yr
In developing countries:
500,000 deaths/yr

Common disease of infants and young children

Question 21

Treatment and prevention of rotavirus

Answer 21

Treatable by oral/IV rehdration

Preventable by available rotavirus vaccines

Question 22

Spread of rotavirus

Answer 22

Fecal-oral
Remain infective for long periods on surfaces
Water, food, respiratory transmission less frequent

SEASONAL

Question 23

Rotavirus: Current Vaccines

Answer 23

RotaTeq (RV5): Pentavalent live bovine rotavirus vaccine
Contains outer capsid proteins of 5 human RV strains made by reassortment with bovine RV genome segments
75% protective against disease, 98% protective against severe disease

Oral, 3 doses (2, 4, 6 months)
Rotarix (RV1): Monovalent live human rotavirus vaccine
Provides cross-protection against other strains
85% protective against severe disease
Oral, 2 doses (2, 4 months)

Interesting that the monovalent still offers good protection

US: # children hospitalized for rotavirus reduced by ~85%

Question 24

What are the adenovirus serotypes that can cause gastroenteritis

Answer 24

40 and 41

In immunocompromised pts we think about it

Question 25

Duration of adenovirus

Answer 25

5-12 days

Question 26

Astroviruses

Answer 26

Small non-enveloped single stranded RNA virus, star-shaped capsomers

Trypsin necessary to activate infectivity

2-8% of diarrheal ds in children

Excreted for prolonged periods in immunocompromised

Person-to-person and foodborne spread

Outbreaks in daycares, nursing homes, school cafeterias, nursing homes