Viral GI Flashcards
infection epidemiology?
a) Sporadic gastroenteritis of infants: usually caused by rotavirus.
b) Epidemic gastroenteritis: Occurs either in semiclosed communities or as a
result of classic food-borne or water-borne pathogens
Mostly caused by Norwalk-like viruses (NLVs).
c) Sporadic acute gastroenteritis of adults: caused by Norwalk-like viruses,
other caliciviruses, rotaviruses, adenoviruses and astroviruses.
symptoms of GI infection?
watery diarrhea and vomiting.
headache, low fever and abdominal cramps (stomachache).
beginning 1 to 2 days post inf. lasting for 1 to 7 days, depending on the virus
type.
toxic diarrheas due to organisms that particularly infect the colonic mucosa?
Shigella
Salmonella
Campylobacter
Clostridium difficile
E. coli
Viruses (little blood)
diarrhea?
seasonal virusses?
Norwalk-like viruses, the main cause of viral gastroenteritis worldwide, have the
highest activity in winter.
Rotavirus and astrovirus infections occur in cooler months.
Adenovirus infections occur throughout the year.
epdemioloy of virus by age?
0 to 5 year old: Rotavirus infections
5 to 15 years old: Adenoviruses and astroviruses
15 + years old: Norwalk-like viruses, adenoviruses and astroviruses
rotavirux vaccine?
Rotarix
common causes of diarrhea in children?
- enterotoxigenic Escherischia coli
- salmonella, shigella
- cholera, other vibrio bacteria
- cryptosporidium
- Giardia lamblia
>50% of cases of viral
- Rotaviruses alone have been estimated to cause 30-50% of all cases
of severe diarrhoeal disease in man. - Adenovirus (40 and 41) are associated with diarrhoeal disease
- “Norwalk” agent (calicivirus) associated with vomiting and diarrhoea
- “Small round viruses” are closely related to the Norwalk agent.
viruss and areas affecrted
those that replicat ein the gi tract and stay there?
adeno
calicivirus
astrocivurs
rota virus
viruses that replicate in gi and move to other tissue?
Picornaviruses
Polio spinal nerves
Coxsackie heart-uterus
Hepatitis A liver
all Adenoviruses
Small ‘naked’-non-enveloped RNA-Viruses: high pH and environmental r
info on rotavirus?
• Human rotavirus, family Reoviridae/ possible animal/bovine reservoir
• Seven human species, referred to as serogroups A to G.
• Rotavirus A - 90% of infections in humans (rest B, C).
• Infects gastrointestinal cells: villi of small intestines (? Others?)
• Isolated from feces, urine, CNS, blood
• Some natural immunity (mother to child antibodies)
• Detection by antigen ELISA, EM< RT-PCR
• Neutralization proteins VP4 (P serotypes) and VP7 (G serotypes)
• Very diverse: 42+ P/G serotype combinations
• Toxic rotavirus protein NSP-4 (first viral enterotoxin) ↑ secretion
>(milk intolerance / lactase deficiency)
• Vaccines: Bovine (Jennerian), human, human/animal reassortants
• 1996-1998 live attenuated rotavirus vaccine Rotashield (quadrivalent)
withdrawn / intussusception
• 2006 two new live oral attenuated rotavirus vaccines: Rotarix
(monovalent) by GlaxoSmithKline/ RotaTeq (pentavalent) by Merck.
Rotavirus (particle size ~70nm), nonenveloped (wheel-like= lt. rota)
ds RNA ; 11 fragments
very stable: pH 3 or 60
o C for 10 h
virus survives in sewage
Human rotavirus is difficult to culture in
vitro (need for trypsin)
Detection by antigen ELISA in stool
viral proteins:
VP2
VP4 - Neutralization antigen
VP6 - Subgroup antigen
VP7 - Neutralization antigen (G Serotype)
Subcore
rotarix?
Monovalent
Rotarix (Glaxo Smith Kline) is a human, live
attenuated rotavirus vaccine containing a
rotavirus strain of VP7- G1 specificity
(monovalent).
ROTARIX is indicated for the prevention of
rotavirus gastroenteritis caused by G1 and
non-G1 types (G3, G4, and G9) when
administered as a 2-dose series in infants
and children.
Oral administration, no side effects observed
in children in 2006 after clinical trials. Clinical
trials ‘in high-mortality, low-socioeconomic
settings of South Africa and Malawi’.
rotashield?
Multivalent
Rotashield (Wyeth) was found to be 80-
100% effective in clinical trials in United
States, Finland, and Venezuela 1996-
1998, with no adverse effects.
Upon roll-out- severe side effects:
intestinal invagination,…=
intussusception observed
in 1: 120000 vaccinees.
Removed from market 1999.
scientific lead?
SCIENTIFIC lead:
Rotashield - rhesus rotavirus
(RRV) parent - human rotavirus
(HRV) reassortant quadrivalent
vaccine with VP7 serotype G1, 2,
3, and 4 specificity from the
human rotavirus parent strain by
Kapikian et al., 1996- not
approved.
Kapikian AZ, Hoshino Y, Chanock RM, Perez-Schael I. Efficacy of a
quadrivalent rhesus rotavirus-based human rotavirus vaccine aimed at
preventing severe rotavirus diarrhea in infants and young children. J Infect Dis
1996;174:S65-72.
Rotavirus, Emerging Infectious Diseases, Vol 4 No 4, Oct 1998.
For RotaTeq (Merck)-Clark and
Offit- 2005,
the parent virus is bovine, with the
bovine attachment protein VP4
(type P7), and 4 human serotypes
G1 to 4) of VP7.
A fifth reassortant virus expresses
the human attachment protein
VP4, (type P1A), and the outer
capsid protein VP7 (serotype G6)
from the bovine rotavirus parent
strain.
