GI Viruses Flashcards
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
Norovirus Clinical Syndrome
Not a serious illness
Incubation period 24 - 48 hrs
Duration of illness: 12 - 60 hrs
Prominent features
- nausea
- nonbloody diarrhea
- vomiting
- abdominal cramps
Children> vomiting; adults> diarrhea
Virus shedding may last for. 3 weeks or more
Duration of illness can last longer ( 4 - 6 d) than previously recognized in young children and elderly adults
Chronic diarrhea in immunocompromised; prolonged virus shedding for months to years
Duration of illness can last longer
Norovirus Outbreak Characteristics
Public health concern
- account for 60 - 90% of nonbacterial food borne and waterborne outbreaks of gastroenteritis
Restaurants are the second most common source for norovirus outbreak
Leading cause of illness from contaminated food
Year round but most common in the winter
Most cruise ship outbreaks
- 90% of diarrheal disease outbreaks on cruise ships are caused by norovirus, virus can persist on surfaces and is resistant to many common disinfectants
Norovirus transmission
Consumption of contaminated food or water
Person to person contact
Contaminated environmental sources
Symptomatic or asymptomatic passengers can bring the virus on board as well
Food: shellfish, salads, celery, frosting, sandwiches, raspberries, cakes etc (those that require handling, but not subsequent cooking)
Water: groundwater supplies, community water systems, swimming pools, recreational lakes, ice
Aerosolization of vomitus; ppl without norovirus can vomit violently without warning
Direct contact: with infectious persons and fomites; secondary transmission
Sick foodhandler is a big deal! Largest food borne outbreaks occurred in Minneapolis St. Paul when a single food handler had vomiting and diarrhea and messed up all the icing
Philly VA nursing home outbreak
Why are norovirus infections so common?
Highly contagious; low infectious dose
Resistant to disinfection; stable in the environment
- resists heat, chlorine, being frozen
Large human reservoir; prolonged virus shedding, even after symptoms resolve
Strain specific immunity is short term and not cross protective
Multiple routes of transmission ( fecal-oral, person to person, infectious aerosol, contaminated food and water)
Strain diversity; genetic plasticity
- norovirus appears to evolve by Ag drift and evading the immune system causing waves of global epidemics much like influenza
Lastly considerable genetic variability exists, because of strain diversity, a person can be infected with norovirus more than once; being infected with 1 type doesnt prevent infx from another type later on
Enteric Adenoviruses
Adenovirus = gland
First isolated from adenoidal tissue
Nondeveloped (Naked)
DsDNA
Icosahedral capsid, composed of three major proteins - herons (serotypes), Peyton’s, and fibers (subgroups)
Adenovirus: classification
Divided into 7 subgroups (A through G)
- based on hemagglutination characteristics (mediated by fiber proteins)
- subgroups with different tissue tropism
57 human serotypes
- characterized by resistance to neutralization by antibodies to other known Adenoviruses
- subgroup F consists of serotypes 40 and 41
- associated with gastroenteritis, especially in infants
- fastidious non cultivatable
- causes 2 - 22% of pediatric diarrhea
Cause endemic diarrhea and outbreaks of diarrhea in hospitals, orphanages, and child care centers; cause 2 - 22% of pediatric diarrhea in inpatients and outpatients
Second to rotavirus in causing pediatric gastroenteritis, they are more important causes of viral gastroenteritis in infants less than 6 mo of age than in older children; infections occur year round with periodic outbreaks
Enteric Adenovirus: Clinical Pearls
Longer incubation period than other enteric viruses
- 8 - 10 days for adenoviruses compared to 1 - 2days for rotavirus, caliciviruses and astrovirus
Diarrhea lasts longer (on avg) than that caused by other viruses
- 8 to 12 days
Occurs year round as well as in epidemics
Less likely to be febrile or dehydrated than children with rotavirus
Unlike other adenovirus types, respiratory symptoms are not prominent
Serotypes associated with mesenteric amenities and intussusception are not the same serotypes that cause gastroenteritis
- 40 & 41 for AGE; 125 and 6 for mesenteric adenitis
Astroviruses
Small round viruses
28-33 nm diameter
Astron = starshaped structure
Distinct star like appearance ( 5 or 6 pt)
SsRNA
Nonenveloped (naked)
Genome includes 3 open reading frames, one encoding the serine protease region, one encoding the RNA dependent polymerase and the third cencoding a polyprotein that is cleaved into the structural capsid proteins
Astrovirus Classification
2 genera in Astroviridae family
- mamastroviruses (mammals)
- astroviruses (birds)
Each genus with multiple species
- 8 serotypes of human astrovirus
- novel astroviruses identified in Washington
- AstV-MLB1, AstV-VA1
Watery diarrhea, vomiting, nausea, in stools of kids
Most diseases affecting young kids but symptoms less severe so you wont see this much at CHOP but you will see norovirus
Astrovirus: Clinical Pearls
Detected in stools of children with diarrhea in a variety of settings
- 2 - 16% in hospital-based studies
- 5 - 17% in community based studies
- outbreaks
Winter peak (like rotavirus) in temperature climates - seasonality less clear in tropical areas
Most disease detected in young children (<2)
- clinical presentation similar to but typically milder than that of rotavirus
- durable immunologic protection
Astroviruses shed in large amounts in the stool, suggest that infection is associated with atleast short term protection against reinfection with the same serotype
Laboratory diagnosis
Usually dont bother with lab tests unless there is an outbreak
Enteric viruses tough to detec
Traditional viral diagnostics do not work well
- GI viruses do not grow well in cell culture
- Ag detection limited; not totally sensitive (only rotavirus an dAdv 40/41)
Much of viral GI disease goes unrecognized
Need more sophisticated methods
Nucleic acid amplification tests (NAAT)
Treatment of gastroenteritis
Self limited in immunologically normal hosts
No specific antiviral therapy
Supportive care- replace fluids to correct electrolyte imbalance and dehydration
Vaccine: live oral vaccine for rotavirus infx
Prevention and Control
Live, oral vaccine for rotavirus
Hand washing and good hygiene
Identify and eliminate a common source
Employ infection control procedures
Clean soiled surfaces and laundry
Stop renewal of susceptible population
Which of the following statements about rotavirus infections is true
A) infx of intestinal tract causes loss of electrolytes and prevents reabsorption of water leading to dehydration
B) infection is spread by respiratory droplets
C) There is no currently licensed live rotavirus vaccine
D) infx in adults are more severe than in children
E) asymptomatic infx do not lead to shedding of the virus in the feces
A
Major difference in epidemiology between Norwalk virus and rotavirus
Norwalk causes disease any age group, rotavirus strikes mainly in children
6 yo boy is coughing, has nasal congestion, fever, headache, chills, and muscular pains
EM examination of throat washes reveals an icosahedral virus that is most likely
Adenovirus - only nonenveloped virus