Flashcards in M- Viral Infections of the Gut and Nosocomial Diarrhea Deck (49):
What are the 2 main viral causes of gastroenteritis?
What are the 2 other frequent viral causes?
1. Rotavirus (peds>adults)
2. Norovirus (older kids and adults > pediatrics)
What populations are most affected by Rotavirus? What disease presentation is in each?
1. Children - acute, severe, dehydrating diarrhea
2. Nursing home residents, other adults
3. Immunocompromised - chronic diarrhea
An HIV + man comes in with chronic diarrhea. What is the likely cause?
Rotavirus- causes chronic diarrhea in the immunocompromised
What family of virus is rotavirus?
What is the structure and genome?
How is the structure protective?
It is a member of the reovirus family.
Structure: It is non-enveloped which makes it resistant to drying, gastric acid, detergent, and disinfectants and thus able to survive in the environment.
Genome: dsRNA with 11 segments coding 12 proteins. It CAN go through reassortment (like influenza but much more rare and less viral variation from year to year.)
Describe what is in the 3 concentric shells of the Rotavirus.
Which is used for classification and serology?
Inner- 1 major protein, polymerase, genome
Middle- VP6 major antigen
Outer (used for classification and serology):
1. surface glycoprotein VP7
2. protease-cleaved protein VP4
There are 7 serogroups for Rotavirus. Which 3 cause disease in humans? Which is primarily associated with children? Adults?
Serogroups A, B and C cause disease in humans.
A = children
B,C = adults
What is the infectious dose of Rotavirus?
How is it spread?
What is the seasonal distribution?
Infectious dose : 10 virions
It is spread by fecal-oral transmission:
- person to person
- fecally infected water and food
There is a winter peak in temporal climates
(year round infection in tropical climates)
Your child goes to a day care and now is having diarrhea. What is your first instinct on the cause?
It is probably from secondary spread of rotavirus.
nfectious dose is low (10 virion) and high dose comes out per ml of stool (10^11)
This makes spread easier in:
- day care centers
- adult caregivers get sick from their kids
How long is the incubation period for Rotavirus?
How long does vomiting usually last?
What other symptoms are present?
What is the duration of the disease?
The incubation period for Rotavirus is 1-3 days and lasts 3-4 days.
The vomiting only lasts for the first day because the rotavirus is a primarily diarrheal disease.
1. watery diarrhea - 20 stools per day (stool leukocytes in a small proportion of patients)
3. mild URI symptoms
What is the pathogenesis of rotavirus?
Where specifically in the GI tract does it infect?
What are the 3 mechanisms by which it causes diarrhea?
It infects cells at the villus tip in the small intestine.
1. lytic destruction of absorptive cells --> fluid leakage from barrier disruption
2. Damaged cells are replaced by immature crypt cells --> malabsporption--> carbs in the lumen--> osmotic diarrhea
3. NSP4 (non-structural protein 4) is a secretagogue--> secretory diarrhea
Describe immunity to rotavirus.
What 2 antibodies appear to be protective?
Immunity is transient and requires repeated exposures to get good immunity.
Immunity is serotype specific, so if a different strain infects you, you will get sick again.
Intestinal IgA appears to be protective
Maternal antibody in breast milk is protective
How do you make the diagnosis of rotavirus?
It is unneccessary to make etiologic diagnosis.
For epidemiological studies or special hosts you could:
-ELISA (chronic diarrhea in immunocompromised)
- Latex agglutination
What is treatment for Rotavirus?
Symptomatic and supportive care like rehydration
There are no antiviral treatments
What is the criteria to receive IV therapy for Rotavirus?
1. intractable vomit
2. altered mental status (unable to follow directions)
3. loss of >10% body weight
How do you prevent rotavirus?
1. handwashing, barrier precautions, isolation of cases
2. adequate sanitation/water treatment
3. Vaccine - RotaTeq and Rotarix
To what viral family does Norovirus belong?
What is the structure and genome?
How does the structure protect the virus?
What is the prototype strain?
It is a Calicivirus.
Structure: it does not have an envelope so it is resistant to detergents, drying out, etc allowing it to spread environmentally.
Genome: ssRNA (+)
The prototype strain is Norwalk virus
What is the infectious dose of norovirus?
How is it spread?
What places are likely to have epidemic outbreaks?
Infectious dose is 10 virion (same as rotavirus)
It is spread by the fecal-oral route
- person to person
First exposure as children but there are secondary and tertiary spread.
Epidemic outbreaks in :
- nursing homes
Describe the disease manifestation of norovirus.
What is the incubation?
What is the most predominant symptom?
What are the other symptoms?
How long does it last?
Norovirus has an incubation of 1-2 days and disease manifestations last about 2-3 days.
The most predominant symptom is VOMIT
Other symptoms: fever, myalgia, diarrhea (8 stool a day vs. 20 with rotavirus)
What is the pathogenesis of Norovirus?
1. shortening/atrophy of villi in prox. small bowel
2. inflammatory infiltrate
3. carb malabsorption --> osmotic diarrhea
What is immunity for Norovirus?
It is short-lived (4 to 6 months) and requires re-exposure to get any type of protection.
Immunity is strain specific, but 50% of adults are immune suggesting high exposure rate
What is diagnosis for Norovirus?
It is usually only presumptive based on clinical grounds and epidemiological context of outbreaks.
Immune serum can agglutinate particles for EM and PCR can be used for epidemiology.
How can rotavirus and norovirus be distinguished clinically?
Rotavirus- diarrheal prominent
Norovirus- vomiting prominence
What is treatment and prevention of norovirus?
2. analgesics, antiemetics
1. provide uncontaminated food/water
2. handwashing & disinfection procedures
3. isolation if necessary
How does prevention of getting rotavirus and norovirus different?
Rotavirus has an effective vaccine, norovirus does not
Who typically gets viral gastroenteritis from adenovirus?
What is incubation and how long does disease presentation last?
What 2 serotypes cause gastroenteritis?
Children in a hospital/institutionalized setting tend to get infected with serotypes 40, 41.
The incubation is about a week and the disease symptoms last 8-12 days
Who is typically infected by astrovirus? What is incubation and duration of the illness?
Astrovirus affects extremes of life : children and elderly
Incubation is 1-4 days and the disease last 1-4 days
What are the major causes of diarrhea in the hospital setting?
What is the most significant?
1. non-infectious vs. infectious
2. Viral (rotavirus, norovirus)
3. Antibiotic associated
4. C. difficile ** this is the most significant bc it has increased morbidity, mortality, hospital stay and healthcare costs
How does C. difficile look on gram stain?
It is a spore forming gram + rod that is strictly anaerobic.
The rods will be purple with dark spots on the ends (the spores)
There are endogenous and exogenous sources of C. difficile. What is meant by this?
What is required for someone to actually get disease from C. difficile?
1. Endogenous- 4% of adults have it in their normal flora (and it can cause problems if it outcompetes)
2. Exogenous- spores can survive for a long time in the environment.
Presence of the toxin is necessary to cause disease
Where are outbreaks likely to occur for:
3. C. difficile
1. daycares (nursing homes, children's hospitals)
2. cruise ships (nursing homes , hospitals)
3. hospitals, nursing homes, on the shoes hands and clothing of health care workers
What is the pathogenesis of CDAD?
1. antibiotic therapy
2. alteration of colonic microflora
3. C. difficile exposure and colonization
4. Release of toxin A and B
5. Colonic mucosa injury and inflammation
What is the biggest risk factor for CDAD?
What are other risk factors?
This biggest risk factor is:
Previous or concurrent antibiotic therapy
severity of underlying disease
H2RB and PPI
duration of hospital stay
What 4 antibiotics have a strong increased risk of developing CDAD?
What 2 have mild association?
1. clindamycin ** notorious for C. difficile
Mild association: pipercillin and ticarcillin
What toxins are associated with C. difficile?
What is their mode of action?
Which is more potent?
It has 2 toxins: A and B
They both bind Rho GTP-binding proteins, dysregulate the cytoplasm by depolymerizing actin, round up, detachmrny apoptosis and cytopathic effects
Toxin B is 10x more potent and is a cytotoxin
Toxin A is a cytotoxin AND enterotoxin (causes secretory diarrhea)
What is the spectrum of clinical entities of CDAD from least bad to worst?
2. antibiotic-associated diarrhea
3. psuedomembranous colitis
4. toxic megacolon
What are three clinical manifestations that should make you think about C. difficile?
1. Elevated peripheral WBC (even before diarrhea)
2. stool positive for occult blood
3. stool leukocytes present
What symptoms are associated with toxic megacolon?
1. ileus - lack of propulsion
2. abdominal distension
4. severe pain
5. radiologic evidence of acute dilation
What causes pseudomembranous colitis?
What is the gross pathology?
What is the microscopic pathology?
C. difficile has cytopathic effects causing friable red mucosa with ulcerations and hemorrhage.
-multiple, elevated whitish-yellow plaques
mucin, fibrin, PMNs and dead enterocytes
How does the patient history differ from CDAD and other antibiotic-associated diarrhea?
CDAD- no relevant history of antibiotic intolerance
Other: history of antibiotic intolerance
How is the diarrhea different from CDAD and other antibiotic-associated diarrhea?
CDAD- colitis, cramps, fever, fecal leukocytes
Other: moderate w/o evidence of colitis
What complications are associated with CDAD that are not associated with other antibiotic associated diarrhea?
CDAD- psedomembranous colitis, toxic megacolon, hypoalbuminemia, relapses
Other: maybe dehydration
When you withdraw implicated antibiotics, what happens if it was CDAD? What happens if it is antibiotic-associated diarrhea from another cause?
CDAD- often persists and progresses
Other: usually resolves
What drugs are contraindicated for CDAD?
What is the current method used at UTSW for diagnosis of C. difficile?
What are the problems with the method?
1. false + because dead c. difficile will test + but are not secreting toxin
2. has to be in clinical context
What is the treatment for C. difficile?
Which drug is more preferred?
Which drug is used for more severe disease?
1. discontinue antibiotics
2. oral metronidazole (preferred because cheaper and no vanc resistance)
3. oral vancomycin - better for more severe disease
When is vancomycin given over metronidazole for C. difficile?
How is vancomycin delivered?
3. intolerance to metronidazole
4. failure to respond to metronidazole after 3-5 days
It must be given orally. IV vancomycin cannot penetrate the gut mucosa to get to the site of infection
What are treatments for relapsed or recurrent C. difficile?
1. cholestyramine- binds toxin
3. IVIG to toxin
4. Stool transplant ****
What are the guidelines for controlling nosocomial C. defficile infection?
1. frequent hand washing with soap and water *** (need to be mechanical so alcohol sanitizer doesnt work)
3. cleaning with sporicidal agents
5. avoid rectal thermometers