GI Viruses Flashcards
(40 cards)
Why is diarrhea so common?
Gut reabsorbs about 98% of the more than 6 L of liquid that enters it every day
If its efficiency is reduced to 96^, this doubles the amount of excreted fluid, so it does not take much to throw things out of balance—> loose stools and diarrhea
Clinical pearls: differential diagnosis
Enteric pathogens classically divide into three categories based on how they affect host GI physiology:
minimally invasive or enterotoxin-secreting: watery diarrhea
- enteric viruses: ETEC, EPEC, EAEC, V cholera, G lamblia, Cryyptosporidium, S aureus, and B cereus
Inflammatory diarrhea (often bloody): Inflammatory or cytotoxic destruction of mucosa of small bowel or colon leading to diarrhea with leukocytes and blood in stool - salmonella, shigella, campylobacter, EIEC, EHEC, C. difficile , E histolytica
Systemic symptoms Penetrate through intact mucosa and access reticuloendothelial system leading to systemic illness (enteric fever syndrome)
- salmonella typhi And yersinia enterocolitica
Viruses that cause gastroenteritis result in watery diarrhea- they are not invasive
Differential diagnosis: acute diarrhea
90% of acute cases have infectious etiology
Viral infx by far the most common in developed countries, usually self-limited, short duration
Bacterial pathogens more commonly cause severe diarrhea more likely to cause bloody diarrhea
Epidemiological clues
- time of year - some pathogens have marked seasonality
- age of pt - children especially young children, are particularly susceptible to GI viruses, some GI viruses rare cause disease in adults
- travel history - ETEC is good example of diarrhea associated with travel; so too are pathogens that are transmitted via contaminated water ( E histolyticaa , GIardia)
- careful exposure history
- vaccination history - think rotavirus
- Hx of Abx use - think C. difficile
- nosocomial - if diarrhea occurs within a hospital setting, C diff becomes important suspect
Features of clinical presentation can be helpful in narrowing the list of possibilities
Viral Gastroenteritis
Caused by variety of viruses; very similar disease
Sudden onset (1 - 2d after infection)
Short duration, usually <1 week
Watery stools (no mucous or blood)
Fecal leukocytes absent or minimal
Stomach flu
Self limited in healthy well nourished persons with normal immune systems
Asymptomatic infx or mild disease very common
Serious disease can occur in those unable to rehydrate
Chronic diarrhea, increased mortality, and prolonged fecal shedding often seen in immunocompromised hosts
Viruses are the cause of most cases of acute infectious gastroenteritis; this is particularly true in developed countries but less so in developing world where bacteria nad parasites play a more prominent role
Worry about dehydration!
Viruses to be covered
Rotavirus - ds RNA
- major cause childhood mortality; incidence decreasing due to vaccine
Adenovirus
- most serotypes cause respiratory infx; 2 cause GI infx
- linear ds DNA
Calciviruses
- norovirus - ssRNA
- major cause of outbreaks in nursing homes, cruise ships etc
- sapovirus - ssRNA
- prob under appreciated
Astrovirus- affect GI tract, no respiratory symmtpoms
All are non-enveloped viruses, stable outside the body and transported via the fecal-oral route
Relative Distribution of Viral pathogens as causes of acute gastroenteritis in children
Pre rotavirus vaccine era
Rotavirus> adenovirus> norovirus> sapovirus
Key epidemiological features, what is the age of incidence and seasonal occurrence of
Rotavirus Adenovirus Norovirus Sapovirus Astrovirus
Rotavirus
- 6 mo to 2 yr children
- winter (temp)
- year round (trop)
Adenovirus
- infants, young children
- year round; Epidemics
Norovirus
- children and adults
- winter peak; year round occurrence
Sapovirus
- children (primarily infants and toddlers) and adults
- year round
Astrovirus
- mainly young children- year round
Children bear the brunt of viral GI disease (exception: Norovirus)
NOROVIRUS IS THE MAJOR CAUSE OF VIRAL GASTROENTERITIS IN ADULTS
Duration:Clinical/ Virological Features
Rotavirus Adenovirus Norovirus Sapovirus Astrovirus
Rotavirus
- incubation: 1 - 2d
- vomiting: 2 - 3 d
- diarrhea: 5 - 8 d
- virus shedding: 8 - 10 d
Adenovirus
- incubation is longest 8 - 10 d
- vomiting: 2 - 3d
- diarrhea 4-12 d
- virus shedding: 8 to 13 d
Norovirus and sapovirus Incubation 1 - 2 d - vomiting, super short: .5-1 d - diarrhea 1 - 2 d or 4 - 6 d in the children and elderly - virus shedding: 1 - 3 wk
Sapovirus Astrovirus - incubation 1 - 2 d - vomiting 1 - 4 d - diarrhea 1 - 4 d - virus shedding - 8 to 19 d
Viral Gastroenteritis Transmission
Fecal oral route from person to person
Contaminated fomites (eg shared eating utensils, surfaces, toys in playrooms, door knobs, elevator buttons, bed rails, toilet seats) - possible bc it is a non-enveloped virus so it is stable on all kinds of surfaces
Contaminated for or water
- food typically in touch with water
- shellfish
Possibly respiratory secretions
Healthcare associated spread common; particularly for rotavirus and norovirus
Transmission of GI viruses is efficient
Physical hardiness of GI viruses
- stable over wide pH and temperature ranges and even after drying, heating, or freezing
- stable on human hands and objects for extended times
High virus concentration in stools
Highly contagious; small infectious dose
Resistant to inactivation by various standard cleaning soles
Not easily inactivated by antiseptic agents that contain high concentrations >40% of alcohols (eg Purell and Lysol) and by bleach
Pathogenesis of viral gastroenteritis
Viral replication occurs in mature enterocytes at the tips of villi of the small intestine
Infection leads to shortening of the villi, exfoliation, elongation of the crypts, and an increase in mononuclear cells in the lamina propria
Pathological changes are usually patchy
Diarrhea is multifactorial, representing a number of viral and host effects. There are malabsorption and secretory components to the diarrhea, as well as effects related to villus ischemia and intestinal motility. NSP4 of rotavirus may even act as an enterotoxin to induce a secretory state
Rotavirus
Leading cause of severe dehydrating diarrhea necessitating hospitalization in infants and young children worldwide
Respiratory enteric orphan
Naked (nonenveloped)
Triple layered icosahedral capsid
Double stranded segmented RNA genome
Resembles wheels slide 14
Rotavirus Serologic Classification
Human disease is mostly A
Groups B - G primarily infect animals; group B and C cause infections in swine but have occasionally been associated with food borne or water borne outbreaks of human disease in China (B) and Japan (C)
Genetic diversity- reassortment between animal and human strains and Ag drift necessitates surveillance and possible future changes in rotavirus vaccine
Rotavirus: morbidity in Us before 2006
3 million cases/yr in Us; 125 mill in developing countries
Nearly every US child infected before 5 y
Responsible for 4 - 5% of all pediatric hospitalizations
Accounted for 50% of AGE hospitalizations during winter months
Rotavirus: Global Epidemiology
Risk of dying from Rotavirus by Age 5y increases as SES decreases
By age 5 nearly every child will have an episode of rotavirus gastroenteritis
Rotavirus Episodes by Age
Severe rotavirus infx occur in infants and children between 4 and 24 months of age
Annual spread of rotavirus
SEasonality in temperate climates; cool, dry weather appears to promote spread
Activity usually starts in the fall in the southwest US and moves sequentially to the northeast US by spring
In temperate climates like the US, rotavirus activity is most prevalent during cooler months of fall winter and spring
Rotavirus Epidemiology
Person may excrete 1 trillion infectious particles/ml of stool
Infants <3. Months old protected by passive maternal antibody
Readily spread in daycare centers, neonatal units, families (~20% of adult household contacts of infected infants will develop symptomatic infx) **
Older children and adults can be infected throughout life, most are subclinical
Chronic diarrhea, increased mortality and prolonged fecal shedding of virus seen in immunocompromised and repeated infx throughout live are subclincial
Rotavirus clinical syndromes
Fever, explosive water diarrhea and vomiting (up to 40 times/day )
- virus replicates quickly—> shortening and blunting of villi and a mononuclear infiltrate into the lamina propria (if polys suspect bacterial infection but mononuclear cell infiltrates are more characteristic of viral)
Rapidly dehydrating
- isotonic dehydration—> balanced depletion of water and sodium causing extracellular fluid loss
Don’t really see fecal leukocytes and blood in stool this is more bacterial
Systemic infection with viremia and spread to extraintestinal tissues sometimes happens, particularly in immunocompromised children
- lymphatic mode of spread
- enteric rotavirus clinical symptoms
- unclear whether vaccine protects against this
Rotavirus Vaccine
Rhesus rotavirus tetravalent vaccine (Rotachield) but withdrawn due to inussusception
Bovine rotavirus pentavalent live vaccine (RotaTeq, Merck) licensed for use among US infants
- live, oral (ready to use)
- 3 doses (2, 4, 6 mo(
- FDA licensed
- G1-4 serotypes
Rotarix
- live, oral, preparation needed
- 2 doses: 2 and 4 months
- FDA licensed
- G1, 3, 4, 9
Safe and effective in children
Must induce mucosal immune response (IgA in lumen of gut) to be protective; intestinal ab but not serum Ab correlate with protection
Herd immunity possible- can be transmitted to non-vaccinated contacts
Estimated to prevent - 45% of deaths due to rotavirus gastroenteritis
Impact of vaccine on rotavirus incidence
2006 vaccination recommended; 72% children vaccinated in 2013
Peak rotavirus season is delayed each year and is less severe
Prior to the vaccine, virtually all children infected by rotavirus
See less and less rotavirus,m peak suppressed in magnitude although still spring seasonality
Family Caliciviridae slide 24
Genetically diverse group
Small round viruses
SsRNA
Nonenveloped (naked)
4 distinct genera
2 human genera
- norovirus- most important
- sapovirus
Single major capsid protein (VPI)
Norovirus and sapovirus infect humans
Noroviruses vs Sapoviruses
Noroviruses
- cup like indentations
- small round structured viruses
- Norwalk virus
- IV (GI, GII, and GIV contain human strain)
- all ages
- vomiting and diarrhea
- high outbreak potential
- transmission: fecal oral; direct person to person, contaminated food, water or fomites; droplet spread from vomitus
Sapoviruses - cup like indentations in EM - Sapporo virus GI-V - children mainly - mild gastroenteritis with less vomiting - low outbreak potential - transmission - fecal-oral direct person to person spread
Both are genetically diverse
Human Caliciviruses
Noroviruses are currently considered the most widely recognized agents of infectious gastroenteritis in adults and older children in both developed and developing countries
- leading cause of viral gastroenteritis ina adults
- second leading cause of severe diarrheal disease in young children worldwide (should pass rotavirus soon)
- responsible for both outbreaks and sporadic disease
Sapoviruses - found in 3# of children hospitalized for diarrhea and 3% of children in day care centers, outbreaks in institutional settings
