5/28- 5 Viral Infections of the GI Tract, Reoviruses, Caliciviruses, Astroviruses, and Enteric Adenoviruses Flashcards
Gastroenteritis def?
Inflammation of the stomach and intestine
(Note: many illnesses not actually associated with inflammation)
Diarrhea def?
Passage of a greater number of stools of decreased form compared with normal
(standard is 3+ unformed stools within 24 hrs)
Dysentery def?
Bloody diarrhea (also often accompanied with pain)
Mechanisms leading to diarrhea?
- Abnormal electrolyte/water transport due to intestinal secretion (toxin-mediated)
- Presence of intraluminal osmotic factors often due to malabsorption (e.g. from disaccharide deficiency like lactose intolerance)
- Disorders of motility (e.g. from nervous system regulation)
[Viruses like norovirus involves all of these mechanisms]
Patterns of viral GIT infections?
Replication in gut lumen with dz occurring at other site:
- Most enteroviruses
- Most adenoviruses
Replication and dz in GIT:
- Rotavirus
- Calicivirus
- Astroviruses
- Enteric Adenoviruses
Diarrhea is the __ leading cause of death worldwide. ___ are primarily affected
Diarrhea is the 3rd leading cause of death worldwide. Children are primarily affected Viral gastroenteritis is a big part of this
(2 billion cases, 18 million hospitalizations, 3 million deaths each year)
What are the major viruses of diarrhea (4)?
- Rotaviruses
- Noroviruses
- Astroviruses
- Adenoviruses 40 and 41 (group F adenoviruses)
In developing countries, which viruses commonly cause diarrhea requiring hospitalization? Parasites?
- Rotavirus (45%)
- ETEC (20%)
- Adenovirus (5-10%)
- Unknown (15-20%)
Parasites: Crytosporidium
In developed countries, which viruses commonly cause diarrhea requiring hospitalization?
- Rotavirus (~45%; old data.. now less b/c of vaccine)
- Norovirus probably #1 by now (historically #2)
- Adenovirus (5-10%)
So less ETEC/unknown than developing world, and no Cryptosporidium; alternatively no norovirus in developing, even though it’s #1 in developed
General incubation period for viruses causing diarrhea?
Brief incubation period
Transmission for viruses of diarrhea?
- Fecal-oral (although there may be fomites in between)
- Possibly aerosol as well
Diagnosis of viruses of diarrhea?
- Difficult to cultivate in vitro
- Abundant excretion of virus in stool
Treatment for viruses of diarrhea?
- No specific antiviral therapy available
- Fluid and electrolyte replacement is essential
- Good hygiene necessary to control
- Rotavirus vaccine licensed
- Candidate vaccine for Norovirus is in development
Question:
All but which one of the following viruses is a significant cause of diarrhea?
A. Norovirus
B. Rotavirus
C. Parainfluenza virus type 3
D. Astrovirus
E. Adenovirus type 41
Answer:
All but which one of the following viruses is a significant cause of diarrhea?
A. Norovirus
B. Rotavirus
C. Parainfluenza virus type 3
D. Astrovirus
E. Adenovirus type 41
Characteristics of Reoviridae?
- Genetic material
- Segmented/nonsegmented
- Enveloped/nonenveloped
- Shape
- Capsid?
- Resistant to?
- Genetic material: dsRNA
- Segmented (can reassort)
- Nonenveloped
- Shape: spherical
- Capsid: double capsid
- Resistant to: acid (can travel through GIT)
Four reoviridae genera known to infect humans?
- Rotavirus
- Reovirus
- Orbivirus
- Coltivirus
What is this?
Reoviridae family
(includes Rotavirus, Reovirus, Orbivirus, Coltivirus)
Rotavirus is in the family Reoviridae.
What are some of the subcomponents of Rotavirus?
How are they grouped?
7 groups identified based on VP6 core antigen (A-G)
- A is the most common in humans (5 serotypes predominate)
Within the Rotavirus Group A family, what are further subdivisons?
What are these based on?
Group A (based on VP6) is the most common and it has 5 group A serotypes based on outer capsid antigens:
- VP4 (P type)–protease-sensitive (cell-attachment protein; initiates virus infection)
- VP7 (G type)– glycoprotein
Antibodies to what neutralize Rotavirus?
Antibodies to VP4 and VP7 (outer capsid antigens) neutralize Group A Rotavirus
What is the most important cause of severe diarrhea in infants and children worldwide? Stats?
Rotavirus (Group A)
- 1/3 of diarrhea hopsitalizations
- 500,000 deaths in children each year
Most primary infection with Group A Rotavirus occurs when?
First 3 years of life
When do epidemics in temperate climates primarily occur?
Tropical climates?
Cooler months in temperate climates
Year-round in tropical climates
Incubation period of Rotavirus?
Short: less than 48 hours
Where does Rotavirus replicate?
In epithelial cells of small intestine
How long is Rotavirus shed?
At least 10 days
Resistance to infection with Rotavirus correlates best with what?
- Serum and intestinal mucosal Ab
- Possibly failure to express some HBGAs
Mechanisms of Rotavirus-induced diarrhea
- Enterocyte destruction -> malabsorption
- Toxic effects of nonstructural viral protein (NSP4) -> Cl secretion
- Activation of the enteric nervous system (in animals, at least)
How soon can antigen be found in the gut following Rotavirus infection?
As soon as 12 hours
What is seen within 24-72 hours of infection with Rotavirus?
Shortening of villi (leading to malabsorptive diarrhea)
How long does it take for villi to lengthen back to normal? Is virus in feces at this time?
7 days after infection (7 dpi)
Virus can be found in stool
Rotavirus Symptoms
- Vomiting, diarrhea, abdominal pain, fever, and dehydration (may be fatal)
- Reinfections typically are milder
- Chronic diarrhea may occur in immunocompromised hosts
- Necrotizing enterocolitis reported
(Often unrecognized in adults; realized when reports went down following vaccines for kids)
Annual impact of Rotavirus in the US before vaccines?
- 400,000 doctor visits
- 200,000 ED visits
- 55,000 - 70,000 hospitalizations
- 20 - 60 deaths
- $300 million direct medical costs
- $900 million in total societal costs
Mortality rates in US vs. developing world (descriptively) due to Rotavirus infection?
- Developed: deaths rare (although high medical burden/cost)
- Developing: high death rate in infants/young kids due to poor nutritional status and other underlying diseases
How is Rotavirus diagnosed?
Antigen detection on stool/rectal swab
- ELISA-based
- Latex agglutination assay
These detect the VP6 of Group A viruses
- EM of stool for non-Group A infections
Treatment/prevention of Rotavirus?
- Rehydration is the mainstay; no antiviral agents
- 2 live attenuated vaccines licensed for infants (1st dose between ages of 6 and 15 weeks)
What are the vaccines available for Rotavirus?
Rotarix:
- Attenuated human strain
- G1 strain for VP7 (most common, 50% of infxns)
- P8 strain for VP4
- 2 doses given at 2 and 4 mo
Rotateo:
- backbone is bovine rotavirus
- G1, G2, G3, G4 strains
- Cow P4 or human P8
- Considered “pentavalent”
- 3 doses given at 2, 4, and 6 mo
Oral rehydration therapy principle? Components?
Principle: active transport of sugar facilitates absorption of salt and water across the gut epithelium
- sodium, potassium, chloride, citrate, glucose
- or table salt, baking soda, orange juice/bananas, sugar
Other human reovirus infections and their vectors and locations?
- Colorado Tick Fever (Colti)–tick vector–(western) N America
Less important:
- Kemorovo–tick vector–W. Siberia
- Orungo–mosquito fector– Africa (causes fever)
- Changuinola–sandfly vector– Panama and S America (causes fever)
Disease caused by Colorado Tick Fever (Colti)?
- Fever
- Myalgia
- Encephalitis
- Hemorrhage
Disease caused by Kemorovo?
- Fever
- Meningitis
Characteristics of Calicivirus:
- Enveloped or non-enveloped:
- Type of genetic material:
- Shape:
- Cultivated in vitro (y/n):
- Enveloped
- ssRNA
- Round (small)
- Not cultivated in vitro
What genera of Calicivirus cause disease in humans?
- Norovirus (9/10)
- Sapovirus (1/10)
Classifications of Norovirus?
Infection depends on what?
3 genotypes cause human infections (many) Genotypes are further divided into genogroups
- Genogroup 1.1 and GII.4 infections depend on blood group H type 1 antigen expression on epithelial cells
Distribution of Norovirus?
- Worldwide
- Seroprevalence rises slowly in childhood and increases rapidly in adults
- Outbreaks in long term care facilities are common
What is the most common cause of acute gastroenteritis in the US?
Norovirus (>90% of viral GE outbreaks; affects all age groups)
- 19-21 million cases/yr
- ~50% of food-borne outbreaks
First Norovirus recognized
Norowok virus (G1.1)
What Norovirus group causes most infections in people worldwide?
GII.4 genotype (only affect “secretor-positive”)
How is norovirus transmitted?
- Food and water; common in shellfish (as Vibrio is for bacteria)
- Person to person
- Droplet spread (after vomiting)
- Common on cruise ships/planes
- Schools, hospitals, nursing homes
For outbreaks of gastroenteritis, need to consider norovirus!
Incubation period for Norovirus?
Short; 1-2 days
Mechanism of diarrhea with Norovirus?
- Shortening of microvilli in small intestine with infiltration of mononuclear cells; causes transient malabsorption and delayed gastric emptying
Immune response to Norovirus?
- Poorly characterized
- Antibodies that block NV-human blood group antigen binding may protect
Symptoms of Norovirus? Timeframe?
- Nausea, vomiting, diarrhea, abdominal cramps, fever, chills, myalgias, and headache
- Can have just vomiting or just diarrhea
- Febrile seizures in infants
- Usually mild and brief illness (1-2 days)
(Although much longer in immunocompromised, such as with organ transplants)
Diagnosis of Norovirus
- Primarily RT-PCR (can detect viral genome)
- Antibody assays and antigen detection not as sensitive
Treatment of Norovirus
- Fluids and electrolytes
- No antiviral therapy
Prevention of Norovirus
- Handwashing
- Disinfection (10% bleach)
- Monitoring of water purification
Other viral agents producing gastroenteritis; common features?
- Geography
- Site of infection
- Mechanisms of immunity
- Occurrence (sporadic, continuous, epidemic)
- Transmission
- Worldwide in distribution
- Probably infect the small intestine
- Mechanism of immunity unknown
- Usually sporadic in occurrence
- Fecal-oral transmission likely
Astrovirus characteristics:
- Enveloped or non?
- Genetic material:
- Number of serotypes:
- Patterns of infection:
- Commonly affected populations:
- Incubation period:
- Clinical symptoms/duration:
- Diagnosis:
Astrovirus characteristics:
- Non-enveloped
- Genetic material: RNA
- Number of serotypes: 8
- Patterns of infection: endemic; outbreak
- Commonly affected populations: infants/children
- Incubation period: 1-2 days
- Clinical symptoms/duration: Gastroenteritis; 4 days
- Diagnosis: EM, EIA (enzyme immunoassay), RT-PCR, Culture
Enteric adenovirus characteristics:
- Enveloped or non?
- Genetic material:
- Number of serotypes:
- Patterns of infection:
- Commonly affected populations:
- Incubation period:
- Clinical symptoms/duration:
- Diagnosis:
Enteric adenovirus characteristics:
- Non-enveloped
- Genetic material: DNA
- Number of serotypes: 2 (40 and 41)- Group F
- Patterns of infection: endemic
- Commonly affected populations: infants/children
- Incubation period: 8-10 days
- Clinical symptoms/duration: Gastroenteritis; 3-11 days (longer than astrovirus)
- Diagnosis: EIA (most likely done in kids), EM, Culture
Approach to pt with acute diarrhea?
History:
- Consider features of illness (severity, duration, type of illness, presence of fever, abdominal pain, dysentery, stool frequency and volume, etc.)
- Consider pt characteristics (age, underlying dz, diet, travel, recent antibiotic use, etc.)
- Illness in family members or contacts
Physical exam:
- Fever, toxicity
- Evidence of dehydration
- Abdominal exam
Stool exam:
- Gross exam for type of diarrhea (watery, mucoid, bloody)
- Microscopic exam for WBC, fat, undigested fibers, parasites
Etiologic agents of infectious diarrhea (3 main categories)?
- Noninflammatory (watery)
- Inflammatory (typ bloody, fecal leukocytes, although may cause watery diarrhea… e.g. not excluded by lack of fecal blood)
- Parasites (inflamm or non inflamm)
Etiologic agents of non-inflammatory diarrhea?
- Vibrio
- E. coli (ETEC)
- C. perfringens
- S. aureus
- B. cereus
- Giardia
- Cryptosporidium
- Rotavirus
- Norovirus
- Astrovirus
- Enteric adenovirus
Etiologic agents of inflammatory diarrhea?
- Shigella
- Salmonella
- Campylobacter
- E. coli (EHEC)
- C. difficile
- E. histolytica
Etiologic agents of parasitic diarrhea?
- Giardia
- E. histolytica
- Cryptosporidium
- Cyclospora
- Strongyloides
- Microsporidium
- Isospora
Treatment for non-inflammatory diarrhea?
- Symptomatic treatment
- Further evaluation if no resolution
- Exception: metronidazole for Giardia (and other parasites)
Treatment for inflammatory diarrhea?
- Culture of stool (+/- cytotoxin assay) to diagnose
- Consider empiric antibiotic therapy for severe illness (although don’t want to do for STEC!!!)
Treatment for parasitic diarrhea?
- Specific antiparasitic therapy is indicated
Question:
- 3 mo child presents to clinic in rural India
- 2 day Hx of diarrhea (frequent watery stools)
- Low grade fever; moderately dehydrated
What is the most likely cause of illness?
A. Norovirus
B. Astrovirus
C. Rotavirus
D. Adenovirus type 5
Answer:
- 3 mo child presents to clinic in rural India
- 2 day Hx of diarrhea (frequent watery stools)
- Low grade fever; moderately dehydrated
What is the most likely cause of illness?
A. Norovirus
B. Astrovirus
C. Rotavirus– most likely for this severity and in India
D. Adenovirus type 5– least likely; not associated with diarrhea
What is this?
EM of Rotavirus
How is diagnosis of Rotavirus typically done in the US?
Antigen immunoassay
Question:
- 24 yo woman presents with 2 day Hx of bloody diarrhea
- Recently traveled to Cancun, where she enjoyed all foods without specific dietary precautions
Which of the following is the least likely cause of her infection?
A. E. histolytica
B. S. sonnei
C. Norovirus
D. E. coli 0157:H7
Answer:
- 24 yo woman presents with 2 day Hx of bloody diarrhea
- Recently traveled to Cancun, where she enjoyed all foods without specific dietary precautions
Which of the following is the least likely cause of her infection?
A. E. histolytica– often seen in travelers, but normally with longer stay than just a few days
B. S. sonnei– most likely due to relatively short stay of cause
C. Norovirus-- not associated with bloody diarrhea
D. E. coli 0157:H7– next least likely
What is this?
Fecal leukocytes IPMNs and others) and RBCs
What is this?
Typical dysentery
- Blood, mucus, small volume
What is this?
Which side is normal?
- Sigmoidoscopic appearance of colon due to Shigellosis
- Left side is normal
What is this?
- Ambeiasis: Cyst and trophozoite (E. histolytica)
What is this?
Rabbit loop assay
- Shows effect of labile toxin of ETEC
- Causes secretion of fluids into intestines
- Inject sample into lumen of rabbit intestine and monitor secretions (will blow up)
Question:
- 46 yo previously healthy man with 2 mo Hx of non-bloody diarrhea (stools greasy and foul-smelling).
Which of the following is the most likely cause?
A. Enterotoxigenic E. coli
B. Campylobacter jejuni
C. Giardia lamblia
D. Bacillus cereus
Question:
- 46 yo previously healthy man with 2 mo Hx of non-bloody diarrhea (stools greasy and foul-smelling).
Which of the following is the most likely cause?
A. Enterotoxigenic E. coli– brief illness, typ over 24 hrs or a few days
B. Campylobacter jejuni– may be longer illness, but not like this
C. Giardia lamblia- classic presentation for this (prolonged illness); hiking
D. Bacillus cereus
What is this?
Scanning EM of trophozoite of Giardia lamblia
What is this?
Giardia: cyst and trophozoites
