Viral GI infections and C. difficile Flashcards
What warning signs are usually absent for viral GI infections that can help distinguish them from bacterial ones?
No high fever, bloody diarrhea, or severe abdominal pain
Which symptom is often most prominent for viral GI infections?
vomiting
What is the typical duration of a viral GI infection?
usually self limiting and over in 72 hours
What are the #1 and #2 causes of viral GI infections worldwide?
- rotavirus
2. norovirus
What family of virus does norovirus belong to?
Caliciviridae
What kind of genome do the Caliciviridae (norovirus) viruses have? what structure?
ssRNA (+) and non-enveloped
What is the clinical presentation for someone with acute gastroenteritis brought on by norovirus?
Explosive diarrhea and vomiting
- either both or just one of them
What is the approximate incubation period for Norovirus?
24-48 hours
What are 4 clinical criteria to diagnose someone with norovirus?
- short incubation period (1-2 days)
- short illness (1-3 days)
- high frequency of vomiting
- absence of bacterial pathogens
How infectious is norovirus? what is the infectious dose?
highly infectious! 1-10 particles only
what is the mode(s) of transmission for norovirus?
- fecal oral
- fomites
- airborne (emesis of vomit)
Once the symptoms of norovirus clear, do patients still shed virus?
Yes for a couple weeks or months (immunocompromised)
What types of foods are often contaminated with norovirus?
shellfish that filter water and concentrate the virus
How many generogroups and subsequent genotypes are there for norovirus?
5 genero groups (GI-GV)
34 genotypes
Which two generogroups of norovirus are the primary cause of human disease
GI and GII
What generogroup/strain of norovirus is most often responsible for outbreaks? How often do new strains of it emerge?
GII.4
New ones every 2-3 years
Can you culture norovirus?
no
How can you test for the presence of norovirus?
antigen detection or molecular detection with RT-PCR
What are two different genetic targets for RT-PCR with norovirus and when would you want to use either one?
Viral RNA dep. RNA pol is good to determine that you HAVE norovirus because they will all have it
Want to look at sequences in more variable regions in order to differentiate between strains of norovirus
What family of viruses does Rotavirus belong to?
Reoviridae family
What is interesting about the structure of rotavirus? (3)
- 11 dsRNA segments
- non-enveloped
- 3 capsids: outer, intermediate, and inner capsid
How many rotavirus particles are required for infection?
as few as 100
How long after a rotavirus infection can you still detect the virus particles?
57 days
What is the mode of transmission for rotavirus?
- fecal oral route
2. food and water borne
What two lab tests are used to detect rotavirus?
- Antigen testing
2. RT-PCR
What is the clinical presentation of rotavirus in children?
- low grade fever
- vomiting (2-4 days)
- Explosive non-bloody diarrhea thats very frequent
What is often the most dangerous result of a rotavirus infection?
Severe dehydration due to repetitive diarrheal episodes
What % of severe gastroenteritis in children is caused by rotavirus?
~25-65%
What % of deaths for children under 5 are caused by rotavirus?
5%
Why was the RotaShield vaccine taken off the market?
Some link to to increase in intussusception of the small intestine
What are the two currently prescribed rotavirus vaccines?
Rotarix™ (GlaxoSmithKline Inc.) and RotaTeq® (Merck Canada, Inc.)
How do the Rotarix and RotaTeq vaccines differ? which is better?
Rotarix: intravenous and monovalent
RotaTeq: oral and pentavalent
- better one
What kind of genome/structure does enteric adenovirus have?
linear dsDNA and non-enveloped
What serogroup of adenovirus causes gastroenteritis? what types?
Serogroup F: types 40 and 41
What is the incubation period of enteric adenovirus ?
3-10 days
What is the duration of illness with enteric adenovirus? is it shorter or longer than rotavirus/norovirus?
longer: 6-9 days
Who is more likely to get infected with enteric adenoviurs?
kids, same as rota
What are the symptoms of an enteric adenovirus infection?
Diarrhea and or vomiting
What is the mode of transmission for enteric adenovirus?
fecal oral route
How is enteric adenovirus detected in the lab?
PCR or antigen testing
What is the genome type/structure of Astrovirus?
ssRNA (+) and non enveloped
What is similar/different between Astrovirus and Rotavirus?
Symptoms are similar but less vomiting, nausea, and fever
Less infectious than rotavirus
How is Astrovirus spread?
fecal-oral route
Where do outbreaks/when do infections usually occur for astrovirus
Mainly kids get it
outbreaks in daycares etc.
How is astrovirus detected?
with RT-PCR
Which of the Hepatitis viruses are bloodborne? Which are water borne?
Hepatitis B, C, and D are bloodborne
Hepatitis A and E are waterborne
What kind of genome do HAV and HEV have?
ssRNA (+)
What type of genome(s) do the bloodborne hepatitis types have?
B&D are dsDNA, HCV is ssRNA(+)
Which of the Hepatitis types are enveloped? which are non-enveloped?
HAV and HEV are non-enveloped
HBV, HDV, and HCV are enveloped
Which two types of Hepatitis are there vaccines against?
HAV and HBV
What family of viruses do HAV and HEV belong to ?
Picornaviridae
What is the incubation period for Hepatitis A?
2-6 weeks
Whats the prognosis of an infection with HAV?
usually self limiting, no chronic disease
What’s the difference between kids and adults in terms of symptom presentation for HAV?
Children (90% asymptomatic)
Adults (0.9% asymptomatic)
How long to symptoms typically last without treatment?
2-6 months
What symptoms are common for an HAV infection?
Fatigue, nausea and vomiting, abdominal pain
Jaundice (yellow skin and eyes)
Dark amber urine (bilirubin excreted in urine)
- can get liver inflammation
Why can you only use PCR early on in disease progression for HAV?
Early in disease, HAV excreted in stool – PCR possible
As it progresses, antibodies are made and you won’t find it in the feces anymore
- usually this it the point at which people are presenting with symptoms
How is a diagnosis with HAV usually made? what is an important differentiation to make in terms of antibodies?
using serology
IgM = acute infection vs. IgG = immunity
What is the route of transmission for HAV and HEV?
fecal oral route
What are the two vaccines available for Hep A and E and how do they differ?
Havrix (A only) and Twinrix (A&B)
How long does it take post-vaccination to establish protection against Hepatitis? How long does it last?
Efficacy 95%, lasts 20 years
Protection in 2-4 weeks
Antigen detection (EIA) can be used for all enteric viruses we discussed (excluding Hepatitis) except for…
astrovirus
What are 4 ways to prevent gastroenteritis?
- Wash hands
- Limit person to person contact
- Remove source of infection
- Decontamination with bleach of environment
What kind of bacteria is C. difficile?
An anaerobic, spore-forming, Gram positive rod
What is C. difficile the major cause of?
Nosocomial infectious diarrhea
What are the 6 stages in development of disease from C. difficile?
- Colonization
- Antibiotic exposure
- Disruption of intestinal microflora
- Proliferation and toxin production
- Damage to intestinal epithelium
- Diarrhea and other diseases
What two genes are required for C. difficile to produce toxin and therefore be virulent?
TcdA and TcdB
How does C. diff colonize the small intestine?
- You ingest bacteria and spores
- the bacteria die in the stomach but the spores survive and make it to the SI
- There they will germinate and attach to the mucosal epithelia
- Multiplication
What is the #1 cause of increased risk to developing C. difficile?
Disruption of normal intestinal microflora by antibiotic use
What does the toxin released by C. difficile do to the epithelial cells of the SI? What does it inhibit specifically? What is the result?
Binds to unknown receptor and is brought in by endocytosis
Inhibits small GTPases
Leads to cytopathic effect of cell rounding which disrupts tight junctions = fluid secretion = diarrhoea
How does the immune response influence the pathogenesis of C. difficile?
Increased inflammation due to neutrophil infiltration which leads to:
Intestinal damage
Impaired permeability
Fluid secretion
What is a common symptom not always caused BY but often occurs with C. difficile infections?
Pseudomembranous colitis
What is Pseudomembranous colitis?
Build up of cell debris and fibrin forming membranous “blisters” throughout the intestine
What is the spectrum of disease for C. difficile associated diseases?
Asymptomatic (colonization) Antibiotic-associated diarrhea (AAD) Pseudomembranous colitis (PMC) Toxic megacolon Death
What is the new, emerging hypervirulent strain of C. difficile called?
NAP-1
- north american pulse field gel type 1
What makes NAP-1 hypervirulent?
a mutation in the regulator gene for the toxin = upregulation of the toxin
What antibiotic is used to treat a non-severe presentation of C. difficile?
Metronidazole
What antibiotic is used to treat a severe presentation of C. difficile?
Oral vancomycin
What has been shown to be a more effective treatment than even some antibiotics?
Fecal transplant
What are two lab techniques that can be used to detect C. difficile?
- culture on selective media
2. Enzyme immunoassays (EIA)
What 3 lab techniques can be used to detect the production of C. difficile toxin (ie. a virulent strain)
- Enzyme immunoassays
- Cell Culture Cytotoxicity neutralization assay (CCCNA)
- Nucleic acid amplification tests (NAATs)
What media/agar is used to culture C. difficile?
Cefoxitin cycloserine fructose agar (CCFA)
What smell is associated with C. diff growing in culture
Barn yard
What “common antigen” is being tested for in an EIA for C. diff?
Glutamate dehydrogenase
What needs to be done after confirming that the sample does contain C. difficile?
Need to do a toxin confirmation test to tell if its the virulent kind
