ICL 1.5: Gastrointestinal Viruses Flashcards
what must GI viruses overcome to survive and cause an infection?
- acidic environment of stomach
- bile salts of upper small intestine
- penetrate mucus coating of gut to bind receptors
what is gastroenteritis?
inflammation of the stomach, small and large intestines
GI infections are 2nd major cause of infectious morbidity worldwide
which cell type do GI viruses infect?
- villus enterocytes = non-dividing, absorptive
- crypt cells = dividing, secretory Cl-
enterocytes are on the outside and crypt cells are father in
`
what is malabsorption?
loss of enterocytes by direct infection.
what is secondary malabsorption?
loss of enterocytes secondary to loss of crypt cells
crypt cells slowly divide and migrate up villus to replace enterocytes
what do gut bacteria do?
there’s 500 different species living in your gut
they aid digestion and regulate gut inflammation
they also protect host from pathogenic bacteria
which virus families cause AVG?
AVG = acute viral gastroenteritis with diarrhea and vomitting
- rotaviruses
- enteric adenovirus type 40, 41
- caliciviruses (sapoviruses, noroviruses)
- astroviruses
what are non-enteropathogenic viruses?
viruses that infect the gut but are not pathogenic in the gut
which virus families are non-enteropathogenic viruses?
- enteroviruses
- cosaviruses
- reovirus
- adenoviruses
viruses that infect the gut but are not pathogenic in the gut
what are opportunistic viruses?
viruses that happen in immunosuppressed hosts
ex. HIV infection of gut with diarrhea or weight loss
what is the incubation of AVG?
1-3 days
how is AVG spread?
fecal-oral spread or possibly respiratory route
fecal-oral route is a route of disease transmission, when the pathogens infecalparticles passing from one host are introduced into theoralcavity of another host
what are the symptoms of AVG?
- abrupt onset of vomiting (1-3 days)
followed by frequent, copious, watery brown stools (5-8 days)
in severe cases, clear stools (rice water stool)
- low grade fever
- projectile vomiting
- epidemic or sporadic outbreaks
what is a major complication of AVG?
dehydration
there’s so much vomitting and diarrhea so people get dehydrated
how do you prevent AVG?
hand washing
what are some of the presenting symptoms of rotavirus?
rotavirus causes AVG = acute viral gastroenteritis with diarrhea and vomitting
- vomiting
- watery diarrhea
- fever
- sudden onset
which population does rotavirus most often effect?
little children
older children have milder diarrhea
what is the structure of the rotavirus?
naked, segmented dsRNA virus
reoviridae family
what does the rotavirus cause?
originates from the hospital!!
it’s a major agent of gastroenteritis and dehydration
what causes diarrhea in rotavirus?
viral nsP4 protein
it’s a viral enterotoxin that causes diarrhea
what gives someone immunity to the rotavirus?
a specific IgA in the gut lumen
or
IgA and IgG antibodies in the colostrum
what is the most common cause of severe diarrhea in children?
rotavirus
it’s the most common cause of severe diarrhea among children, with hospitalization of ~55,000 children/year in USA and the death of 600,000 children annually worldwide
what is the incubation period of the rotavirus?
about 2 days
what is the progression of the rotavirus?
incubation for 2 days
then vomiting and watery diarrhea for 3 - 8 days
fever and abdominal pain occur frequently too
immunity after infection is incomplete, but repeat infections tend to be less severe than the original infection
during what time of the year does rotavirus peak?
winter months
and in kids
how many strains of the rotavirus are there?
7: A-G
A-C are human viruses
what is rotavirus A?
human virus
effects infants less than 24 months of age
older children have milder diarrhea
in undernourished children-diarrhea and dehydration
can cause death
what is type B rotavirus?
viruses infect humans and swine
associated with outbreaks of diarrhea in older children, adults in China
what is type C rotavirus?
disease in adults/children in Asia
how do you diagnose rotavirus?
- EM
fecal supernatants are incubated with virus-specific antibodies
their ability to cause clumping of virus particles identifies the presence of specific antigens (proteins) and thereby identifies the virus
- RT-PCR
how do you treat rotavirus?
- RotaTeq vaccine = live, oral, pentavalent
- Rotarix vaccine = human, live attenuated, rotavirus
strain of G1P[8] specificity
Rotarix and RotaTeq trials in Africa and Asia found that the vaccines dramatically reduced severe disease among infants in developing countries, where a majority of rotavirus-related deaths occur
Rotavirus Flashcard: what is the virus family, pathogenesis, clinical symptoms, diagnosis and treatment/prevention of rotavirus?
Virus: Reoviridae, segmented dsRNA genome, naked virion
Pathogenesis: Fecal-oral infection, also infects respiratory route, viral nsP4 is a viral enterotoxin, affects children
Clinical: Most common cause of severe diarrhea in children, incubation ~2 days, seven antigenic types (A-G) – (A-C) are human viruses
Diagnosis: Immuno-EM and RT-PCR
Treatment and Prevention: Rotateq and Rotarix vaccines
what is the structure of the adenovirus?
naked, linear dsDNA virus
what is the pathogenesis and clinical features of the adenovirus?
AVG in infants
involution of part of the intestine is a complication
virus infects Peyer’s patches
how do you treat adenovirus?
antibodies are essential for recovery but there’s no treatment or prevention….
how do you diagnose adenovirus?
ELISA assays to detect viral antigens or antibodies
Adenovirus 40 & 41 Flashcard: what is the virus family, pathogenesis, clinical symptoms, diagnosis and treatment/prevention of adenovirus?
Virus: dsDNA genome, naked virion
Pathogenesis and clinical: AVG in infants, infects Peyer’s patches
Diagnosis: ELISA
Treatment and Prevention: None
rotavirus vingette
A 9-month-old baby girl was brought to the emergency department of a local general hospital during the winter with a 2-day history of vomiting, watery diarrhea and fever.
The patient had been well until 24 hours before her presentation, when she had experienced the acute onset of vomiting followed by multiple episodes of diarrhea. She refused to eat, and she drank very little fluid. Her parents were concerned about dehydration. The family had not traveled outside the US recently, but the mother related that she had been leaving her baby in a day care center for 3 days a week for the past 3 months.
which viruses are part of the caliciviridae family?
- norovirus
- sapovirus
- lagovirus
- vesivirus
- sapporovirus
- norwalk virus
norovirus case study
Within 48 hours of a college football game in Philadelphia, 158 students with symptoms of gastrointestinal disease visited the university health service. The predominant symptoms included nausea in 99%, vomiting in 75%, diarrhea in 48%, and headache, fever and myalgias. Marching band members, football players. And faculty and staff from both universities had similar symptoms. A total of several hundred individuals were afflicted with similar symptoms.
what is the structure of the caliciviridae family?
small, (+) RNA naked virus
how are caliciviruses transmitted?
- fecal-oral route like via contaminated food/water
2. aerosol
which caliciviruses are associated with gastroenteritis?
sapoviruses and noroviruses are etiologic agents of human gastroenteritis
who does the Norwalk virus effect?
it’s in the Caliciviridae family
it effects older children and adults
it’s known as the cruise ship virus
what is the pathogenesis of the calicivirus? symptoms?
it infects the intestinal brush border and prevents proper absorption of water and nutrients
this causes diarhea, vomiting, abdominal cramps, nausea, headache, malaise and fever
no seasonal incidence
how do you diagnose calicivirus?
ELISA assays to detect viral antigens or antibodies
how do you treat caliciviruses?
no vaccines or antivirals…
Calicivirus Flashcard: what is the virus family, pathogenesis, clinical symptoms, diagnosis and treatment/prevention of calicivirus?
Virus: Caliciviridae, small, (+) RNA, naked (cup-like projections)
Pathogenesis: Fecal-oral and aerosol transmission, AVG pathogen
Clinical: Infects intestinal brush border cells, Diarrhea, vomiting, abdominal cramps, nausea, headache, malaise and fever
Diagnosis: ELISA
Treatment and Prevention: No vaccine
what’s the structure of astroviruses?
small, (+) strand naked virions
what are the clinical features of astroviruses?
outbreaks of diarrhea in children
peaks in winter in US
how do you diagnose astroviruses?
ELISA assays to detect viral antigen or antibodies in patient specimens
what is the structure of picornaviridae?
small, naked (+) strand RNA virions
what are the three classes of picornaviridae?
- Hepatitis A
- Rhinovirus
- Enterovirus
enteroviruses = acid stable and stable at 37 C
- polioviruses
- coxsackie A and B
- ECHO virus
- vosaviruses
non-GI tract effecting viruses = stable at 33 C but not in acid
- rhinovirus
- heparnavirus
Which viruses are enteroviruses? in what environments are enteroviruses stable?
- Polio viruses
- Echovirus
- Coxsackie A and B
37 C
acid stable = survive in stomach acid
what is the clinical presentation of enteroviruses?
broad disease spectrum = wide range of clinical outcomes
but usually this is the most unapparent infection with no symtpoms…
Enteroviruses are the #1 cause of severe aseptic meningitis = meningitis caused from non-bacterial organism = glucose levels are normal but protein levels are elevated —> kids are really susceptible
Can also cause myocarditis
how do you diagnose picornaviridae?
typed by neutralization of infectivity with specific Abs
virus isolation; detect a specific rise in antibody levels (acute/convalescent titers); IgM capture ELISA; by RNA sequences (RT-PCR) of virus genome/mRNA recovered from patient samples
how is picornavirus spread?
fecal-oral spread/secretions
the virus sheds in feces for weeks…
the feces end up in food or water or the hands of kids and ends up in the mouth
this is why picornaviruses need to be acid stable! So Hepatitis A, polio, echovirus, and coxackie A&B are all acid stable
**only the rhinovirus is transmitted through the respiratory route
how can you prevent picornavirus?
hand washing inhibits transmission cycle!
it’s usually spread via fecal-oral route
what time of the year is picovirus most common?
several serotypes circulate each year
but there’s a summer/fall peak
Think of the peak animal nursery; people would only go during the summer and fall
which cells does polio infect?
virus infects lymphoid cells in pharynx (tonsils) to intestines (Peyer’s patches) to feces
Peyer’s patches are where the virus replicates and it takes 2-3 weeks
in some patients, the infection goes from GI to a primary viremia = virus in the blood –> the virus then spreads to the liver, heart, spleen resulting in increased amounts of virus reintroduced into the blood = secondary viremia
the higher levels of virus contribute to the virus crossing the blood-brain barrier and infecting neurons in the CNS = paralysis
what are the clinical features of polio?
90% of infections are asymptomatic (2-3 days)
- aseptic meningitis
- asymmetric flaccid paralysis; usually concentrated in the legs
- brain stem infected = Bulbar polio
- paralytic poliomyelitis in 1% of infections
- myalgia
- respiratory insufficiency if the paralysis effects the lungs= biggest cause of death in polio patients
what is Bulbar polio?
brain stem is infected
paralysis of cranial nerves, muscles of respiration
how do we prevent polio?
- a trivalent vaccine against 3 serotypes
immunity to each serotype is needed for full protection
- Pediarix
There is no treatment!!
what kind of vaccine is the polio vaccine?
2 versions
- a live attenuated vaccine = Saban vaccine
Given orally; it mimics natural course and route of infection, leads to mucosal IgA immunity
- killed vaccine = Salk vaccine
Given IM, only leads to IgG immunity
*We use the killed vaccine in the US
what are the advantages and disadvantages of the live attenuated polio vaccine?
PROS
1. attenuated and can increase antigen dose
- there is limit to virus production (mutations reduce replication, virion stability)
- oral live form makes both IgG and IgA antibodies!
- since this contributes to herd immunity (unintended infection of others), it benefits at the community/regional level
CONS
1. live vaccine can be shed in the feces and possibly revert to a form that can cause paralysis in another person
how is the killed polio vaccine administered and what does it do?
Aka Sulk vaccine
it is administered intramuscular (IM)
Since it bypasses GI tract since its an injection it only forms IgG antibodies and no IgA antibodies which is the primary antibody in mucosal surfaces
antigen dose is fixed = no replication
current recommendation is 3-4 doses
what is Pediarix?
used to treat polio
it’s a combination product containing DTaP, hepatitis B, and inactivated polio vaccines
it’s licensed for children 6 weeks through 6 years of age
what is VAPP?
VAPP = vaccine-associated paralytic polio
VAPP is clinically indistinguishable from paralytic poliomyelitis caused by wild-type polioviruses and occurs within 60 days of OPV exposure
Poliovirus Flashcard: what is the virus family, pathogenesis, clinical symptoms, diagnosis and treatment/prevention of poliovirus?
Virus: Picornaviridae, enterovirus genus, + ss RNA
genome, naked virion
Pathogenesis: infects lymphoid cells in pharynx -to intestines – to feces, primary and secondary viremia, can cross blood-brain barrier
Clinical: paralytic poliomyelitis, aseptic meningitis, asymmetric flaccid paralysis
Diagnosis: not done
Treatment and Prevention: vaccine trivalent (3 serotypes), live attenuated (Sabin) and heat killed (Salk)
what are cosaviruses?
second most common human enteric infections
new genus of enteroviruses
what is the structure of coxsackieviruses?
(+) RNA, naked virions
what are coxsackieviruses?
Coxsackie A: 23 serotypes
- herpangina (vesicular pharyngitis)
- hand, foot and mouth disease (vesicles) *type A16
- congenital heart disease newborns
- aseptic meningitis
Coxsackie B: 6 serotypes
- pleurodynia (epidemic myalgia)
- acute infectious myocarditis (50% mortality in infants)
- acute pericarditis
what are ECHO viruses?
enteric, cytopathogenic, human orphan - 32 serotypes
can be isolated from “normal” patients
ECHO viruses cause diseases similar to Coxsackie but its infections tend to be less severe than Coxsackie infections
what are enteroviruses 68-71?
EV #70: acute hemorrhagic conjunctivitis (associated also with some infections by Coxsackie A24)
EV #71: is associated with hand, foot and mouth disease (outbreak of vesicles in these locations) in children
which virus families are nonenteropathogenic?
enteroviruses
reovirus
some adenoviruses
which virus families cause diarrhea and vomiting?
rotaviruses
enteric adenovirus types 40 and 41
caliciviruses (sapoviruses, noroviruses)
astroviruses
Which virus is the primary cause of the common cold?
Rhinovirus
How is the rhinovirus transmitted?
Even though it’s a picovirus, it is NOT transmitted through the fecal-oral route
It’s an upper respiratory infection which makes sense because it causes the common cold
What is the structure of the polio virus? What family does it belong to?
Part of the Picornavirus family —> enterovirus subtype
(+) sense, naked ssRNA virus
How is poliovirus transmitted?
It’s a picovirus so it’s transmitted via the fecal-oral route
In order for the virus to do so, it needs to be able to handle the acidic conditions in the stomach —> polio is an acid stable virus!
