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Flashcards in Viral GI Deck (18):

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


toxic diarrheas due to organisms that particularly infect the colonic mucosa?

Clostridium difficile
E. coli
Viruses (little blood)



A image thumb

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?



common causes of diarrhea in children?

1. enterotoxigenic Escherischia coli
2. salmonella, shigella
3. cholera, other vibrio bacteria
4. cryptosporidium
5. Giardia lamblia


>50% of cases of viral


1. Rotaviruses alone have been estimated to cause 30-50% of all cases
of severe diarrhoeal disease in man.
2. Adenovirus (40 and 41) are associated with diarrhoeal disease
3. "Norwalk" agent (calicivirus) associated with vomiting and diarrhoea
4. "Small round viruses" are closely related to the Norwalk agent.


viruss and areas affecrted

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those that replicat ein the gi tract and stay there?




rota virus


viruses that replicate in gi and move to other tissue?


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:


VP4 - Neutralization antigen


VP6 - Subgroup antigen

VP7 - Neutralization antigen (G Serotype)




Rotarix (Glaxo Smith Kline) is a human, live
attenuated rotavirus vaccine containing a
rotavirus strain of VP7- G1 specificity
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 (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?

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
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
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



RotaTeq (Merck) live, oral pentavalent vaccine. The rotavirus A
parent strains of the reassortants were isolated from human and
bovine hosts.



adenoviruses, non-enveloped,
ds DNA (~30 kbp)
very stable: pH 3 or 60
oC for 10 h
Adenoviruses causing gastroenteritis belong
to the serogroups 40 and 41 and do not
grow well in cell cultures.
Adeno virus 40, 41
No treatment, no vaccine
Adenoviruses can be isolated from stools, as well
as throat and respiratory swabs and secretions.
Adenovirus in stools can be detected by latex
agglutination of adeno-antigen and adenovirusspecific PCR. Epidemiology by RE analysis.
Apart from types 40/41, all other adenoviruses (eg
serotype 8 causing epidemic keratoconjunctivitis)
may be found in stools as well.


norovirus detection?

Electron Microscopy (EM)-up to 2002
Requires at least 10e6 Virus particles per g of stool.
Completed in 1 day
100 nm

RT-PCR 1996-2002
GI virus PCR product 150bp,
GII virus PCR product 113bp.
Assay completed in 2 days.

NASBA from 2002
Three primers used based on Ni/E3 and JV12.
Product labelled with Ruthenium,
detected by electrochemiluminesense (ECL).
Assay completed in 1 day