Environmental transmission of norovirus gastroenteritis

Article · February 2012with70 Reads
DOI: 10.1016/j.coviro.2011.11.005 · Source: PubMed
  • 43.7 · Centers for Disease Control and Prevention
  • 18.28 · U.S. Department of Health and Human Services
  • 20.48 · Centers for Disease Control and Prevention
  • 42.32 · Centers for Disease Control and Prevention
Abstract

The advent of molecular techniques and their increasingly widespread use in public health laboratories and research studies has transformed the understanding of the burden of norovirus. Norovirus is the most common cause of community-acquired diarrheal disease across all ages, the most common cause of outbreaks of gastroenteritis, and the most common cause of foodborne disease in the United States. They are a diverse group of single-stranded RNA viruses that are highly infectious and stable in the environment; both symptomatic and asymptomatic infections are common. Through shedding in feces and vomit, norovirus can be transmitted directly through an array of routes: person-to-person, food or the environment. The relative importance of environmental transmission of virus is yet to be fully quantified but is likely to be substantial and is an important feature that complicates control.

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Environmental
transmission
of
norovirus
gastroenteritis
§
Ben
Lopman
1
,
Paul
Gastan
˜
aduy
1,2
,
Geun
Woo
Park
1
,
Aron
J
Hall
1
,
Umesh
D
Parashar
1
and
Jan
Vinje
´
1
The
advent
of
molecular
techniques
and
their
increasingly
widespread
use
in
public
health
laboratories
and
research
studies
has
transformed
the
understanding
of
the
burden
of
norovirus.
Norovirus
is
the
most
common
cause
of
community-
acquired
diarrheal
disease
across
all
ages,
the
most
common
cause
of
outbreaks
of
gastroenteritis,
and
the
most
common
cause
of
foodborne
disease
in
the
United
States.
They
are
a
diverse
group
of
single-stranded
RNA
viruses
that
are
highly
infectious
and
stable
in
the
environment;
both
symptomatic
and
asymptomatic
infections
are
common.
Through
shedding
in
feces
and
vomit,
norovirus
can
be
transmitted
directly
through
an
array
of
routes:
person-to-person,
food
or
the
environment.
The
relative
importance
of
environmental
transmission
of
virus
is
yet
to
be
fully
quantified
but
is
likely
to
be
substantial
and
is
an
important
feature
that
complicates
control.
Addresses
1
Division
of
Viral
Diseases,
National
Center
for
Immunization
and
Respiratory
Diseases,
Centers
for
Disease
Control
and
Prevention,
Atlanta,
GA,
United
States
2
Epidemic
Intelligence
Service,
Centers
for
Disease
Control
and
Prevention,
Atlanta,
GA,
United
States
Corresponding
author:
Lopman,
Ben
(blopman@cdc.gov)
Current
Opinion
in
Virology
2012,
2:96–102
This
review
comes
from
a
themed
issue
on
Environmental
virology
Edited
by
Christiane
Wobus
and
Helen
Nguyen
Available
online
11th
December
2011
1879-6257/$
see
front
matter
Published
by
Elsevier
Ltd.
DOI
10.1016/j.coviro.2011.11.005
Burden
of
norovirus
disease
Endemic
disease
Globally,
norovirus
is
estimated
to
account
for
12%
(95%
CI
915%)
of
community-based
or
clinic-based
gastro-
enteritis
cases,
and
11%
(95%
CI
814%)
of
emergency
department-based
or
hospital-based
cases
[1].
These
pro-
portions
are
similar
in
developing
and
developed
country
populations
[1].
Community-based
cohort
studies
using
sensitive
diagnostics
have
been
rare,
but
such
studies
in
England
and
The
Netherlands
have
estimated
incidence
in
the
general
population
between
4.1
and
4.6
cases
per
100
person-years
[2,3
],
with
regional
studies
providing
generally
consistent
results
[4,5].
Incidence
is
approxi-
mately
5
times
higher
in
children
under
the
age
of
five
years
[5].
In
the
United
States,
norovirus
causes
an
estimated
21
million
cases
of
acute
gastroenteritis
[6]
and
>70
000
hospitalizations
annually
across
all
age
groups
[7].
The
burden
of
disease
increases
considerably
in
years
where
novel
genogroup
II
genotype
4
variants
emerge,
with
hospitalizations
surging
by
approximately
50%
[810].
Although
symptomatic
norovirus
infections
are
usually
mild
and
self-limiting
in
otherwise
healthy
adults,
they
may
be
fatal
among
the
elderly
[11]
and
immunocompromised
persons
[12].
Excess
mortality
associated
with
norovirus
has
been
documented
in
a
number
of
countries
[13,14,11],
with
approximately
800
per
year
in
the
U.S.
[15].
Epidemic
disease
Noroviruses
are
the
leading
cause
of
outbreak-associated
gastroenteritis
worldwide,
causing
50%
of
all-cause
and
more
than
90%
non-bacterial
epidemic
gastroenteritis
[16].
Outbreaks
occur
in
various
settings,
including
hos-
pitals,
nursing
homes,
restaurants,
childcare
centers,
and
cruise
ships.
Although
initial
reviews
of
norovirus
out-
breaks
in
the
U.S.
implicated
contaminated
food
as
the
main
vehicle
of
infection
[17],
newer
reports
show
that
the
majority
involve
person-to-person
transmission
in
the
United
States
and
elsewhere
[1821].
Moreover,
given
the
high
infectivity
and
environmental
stability
of
nor-
ovirus,
transmission
during
outbreaks
may
involve
multiple
routes
[22],
and
contaminated
fomites
may
also
act
as
a
reservoir
and
perpetuate
outbreaks
[2325].
Economic
burden
Few
studies
have
quantified
the
healthcare
or
societal
costs
due
to
norovirus,
but
given
its
ubiquitous
nature,
its
economic
impact
is
likely
substantial.
Most
studies
to
date
have
quantified
the
cost
of
outbreaks,
as
opposed
to
endemic
disease.
For
example,
an
outbreak
in
a
single
946-bed
U.S.
hospital
cost
an
estimated
$650
000
[26].
During
the
20022003
season,
the
cost
to
the
English
National
Health
Service
of
nosocomial
outbreaks
was
estimated
at
$184
million
[27].
Norovirus
foodborne
dis-
ease
in
the
U.S.
leads
to
an
estimated
$2
billion
in
cost
of
illness
annually
[28].
While
endemic
disease-related
costs
have
not
been
systematically
assessed,
norovirus
associ-
ated
hospitalizations
specifically
have
been
estimated
at
nearly
$500
million
every
year
in
the
U.S.
[7].
§
Disclaimer:
The
findings
and
conclusions
in
this
report
are
those
of
the
authors
and
do
not
necessarily
represent
the
views
of
the
Centers
for
Disease
Control
and
Prevention.
Available
online
at
www.sciencedirect.com
Current
Opinion
in
Virology
2012,
2:96102
www.sciencedirect.com
Page 1
Author's personal copy
Environmental
transmission
Norovirus
is
spread
by
a
number
of
routes,
with
both
fecal-oral
and
vomit-oral
transmission
occurring
(Figure
1).
Direct
person-to-person
transmission
is
believed
to
be
the
primary
mode
of
spread
in
most
out-
breaks
[19,21]
and
in
sporadic
disease
[29,30].
Foodborne
transmission
is
also
common,
with
norovirus
the
most
common
cause
of
foodborne
disease
outbreaks
in
the
U.S.
[31,32].
Contamination
of
food
products
by
infected
food
handlers
is
thought
to
be
the
most
common
pathway
[33].
Numerous
waterborne
outbreaks
have
been
reported
but
likely
represent
only
a
small
fraction
of
all
disease.
While
norovirus
has
been
detected
in
sewage
[34,35],
its
role
in
transmission
is
uncertain.
Many
factors
may
facilitate
environmental
transmission
of
norovirus
(see
Box
1).
While
few
data
clearly
demonstrate
the
role
of
environmentally
mediated
transmission
in
the
spread
of
norovirus,
the
most
convincing
evidence
comes
from
outbreaks
where
groups
in
a
common
setting
with
no
known
direct
contact
have
been
sequentially
affected
[36].
Perhaps
the
clearest
such
example
comes
from
an
outbreak
involving
a
single
aircraft
[37

].
After
a
vomit-
ing
incident
on
an
a
long-haul
flight,
flight
attendants
working
on
the
aircraft
on
8
flight
sectors
over
6
days
developed
gastroenteritis.
A
rare
genotype
of
norovirus
was
detected
in
specimens
from
multiple
crew
members.
Working
in
the
contaminated
cabin
environment
was
the
only
apparent
exposure;
no
opportunities
for
person-to-
person
transmission
were
identified.
Another
compelling
example
comes
from
an
outbreak
linked
to
a
concert
hall
[38].
In
the
5
days
after
a
concert
attendee
vomited
in
the
hall,
more
than
300
people
developed
gastroenteritis.
The
highest
risk
was
among
people
seated
closest
to
where
the
vomiting
incident
occurred.
An
analogous
situation
was
recorded
on
a
cruise
ship,
where
6
consecutive
cruises
were
affected
[22].
In
that
outbreak,
however,
there
was
also
widespread
person-to-person
transmission
and
the
possibility
that
crew
members
carried
the
virus
over
between
cruises.
Outbreaks
with
multiple
modes
and
complex
chains
of
transmission
are
probably
the
norm
in
semi-closed
settings
where
groups
of
people
congre-
gate,
live
and
eat.
Virus
may
also
be
easily
transferred
between
hands
and
surfaces
[39],
thereby
facilitating
the
complete
environ-
mentally
mediated
transmission
cycle.
Noroviruses
are
highly
infectious,
with
an
ID
50
between
18
and
10
3
virus
particles
[40

],
so
even
low-level
contamination
may
pose
a
transmission
risk.
Norovirus
has
a
short
incubation
Environmental
transmission
of
norovirus
gastroenteritis
Lopman
et
al.
97
Figure
1
Routes
of
transmission
of
norovirus
from
infected
to
uninfected
people.
Uninfected person
Host factors related to susceptibility
-Acquired immunity
-Genetic susceptibility
-FUT2
secretor status
-Behavior
-Hand hygiene
Environment
Food
Water
Direct
Person-to-person
Infected person
Host factors related to transmissibility
-Symptomatic/asymptomatic infection
-Presence of vomiting
-Behavior
-Hand hygiene
-Social distancing
-Food handling
Disinfection
Current Opinion in Virology
Norovirus
transmission
can
occur
via
a
range
of
transmission
routes.
Characteristics
and
behaviors
of
the
infected
host
and
potential
susceptibles
may
mitigate
the
risk
of
transmission.
This
simple
schematic
is
not
meant
to
depict
all
the
intricacies
of
each
pathway,
but
rather
to
highlight
the
interaction
of
the
various
routes
and
to
illustrate
that
all
pathways
require
shedding
of
virus
from
infectious
hosts.
Different
control
measures
may
be
targeted
at
each
arrow;
here,
the
role
of
environmental
disinfection
is
highlighted.
Certain
practices
(such
as
hand
hygiene)
may
reduce
transmission
through
all
pathways
while
targeted
interventions
(such
as
exclusion
of
ill
food
handlers
from
work)
may
reduce
transmission
through
specific
pathways.
www.sciencedirect.com
Current
Opinion
in
Virology
2012,
2:96102
Page 2
Author's personal copy
period
and
potentially
long
infectious
period
[41,42].
So,
practically
speaking,
in
an
outbreak
setting,
it
is
very
difficult
to
know
who
acquires
infection
from
whom,
since
transmission
may
be
direct
(and
of
short
interval
between
cases)
or
environmentally
mediated
(with
a
serial
interval
up
to
several
weeks)
(see
Figure
2).
Understanding
the
relative
importance
of
direct
versus
environmentally
mediated
transmission
will
help
to
target
control
measures,
which
at
present
are
broad
and
based
on
gen-
eral
food
safety
and
infection
control
principles
[33,43].
Environmental
contamination
Widespread
contamination
of
environments
during
out-
breaks
has
been
documented,
particularly
in
hospital
settings.
Noroviruses
are
hardy
and
have
been
detected
on
environmental
surfaces
during
non-outbreak
periods,
and
non-outbreak-related
strains
have
been
detected
on
environmental
surfaces
during
outbreaks,
so
the
role
of
this
contamination
is
not
clear
[44

,45

].
In
a
series
of
studies,
Gallimore
et
al.
detected
contamination
of
sur-
faces
including
switches,
televisions,
cellular
phones,
public
phones,
water
taps,
toilet
light
switches,
micro-
wave
ovens,
keyboards,
bed
frames
and
chairs
[46

,47

].
Contamination
of
keyboards
and
computer
mice
was
detected
in
one
school
outbreak,
along
with
epi-
demiological
evidence
of
their
role
in
transmission
[23].
Although
the
highest
levels
of
contamination
probably
occur
on
surfaces
directly
contaminated
by
vomitus
or
feces,
virus
has
been
detected
on
mantle
pieces
and
light
fittings,
located
above
1.5
m
in
a
hotel
affected
by
an
outbreak
[24].
This
observation,
together
with
epidemio-
logic
data,
suggests
that
vomiting
accelerates
and
magnifies
spread
of
norovirus
[42,48].
Fortunately,
data
suggest
that
enhanced
cleaning
procedures
reduce
the
98
Environmental
virology
Box
1
Factors
that
promote
the
environmental
transmission
of
norovirus.
Factor
Evidence
Key
references/examples
Large
human
reservoir
Incidence
in
developed
countries
is
approximately
5%
per
year
for
all
ages
and
20%
per
year
in
children
under
the
age
of
5
years.
[2,3
,4,6]
Copious
shedding
in
feces
Peak
shedding
is
typically
10
5
10
9
particles/g
of
stool,
but
may
be
as
high
as
10
11
.
[72,73]
Widespread
and
rapid
dissemination
by
vomit
Settings
were
outbreaks
are
occurring
may
be
widely
contaminated
and
virus
can
be
found
on
a
range
of
surfaces.
Outbreaks
spread
rapidly
due
to
aerosolization
of
virus
via
vomitus,
which
also
serves
to
contaminate
environments
for
future
exposures.
[42,46

,47

,24,48,7275]
Prolonged
shedding
In
experimentally
infected
adults,
virus
can
be
detected
for
a
median
of
4
weeks
and
up
to
8
weeks
(by
RT-PCR).
Virus
can
be
detected
for
up
to
three
weeks
after
the
onset
of
symptoms
in
approximately
25%
of
community-acquired
infections.
[48,72,76]
Environmental
stability
On
the
basis
of
observations
made
in
outbreaks,
norovirus
particles
may
remain
infectious
for
two
weeks
on
environmental
surfaces
and
over
2
months
in
water.
Cool,
dry
conditions
appear
to
be
most
favorable
for
survival
of
infectious
virus.
[48,52
,59]
Resistance
to
chemical
disinfection
Chemical
disinfection
of
surfaces
is
a
key
point
of
the
transmission
cycle
for
intervention,
but
due
to
the
absence
of
an
infectivity
assay
for
human
norovirus,
determining
the
effectiveness
of
various
chemicals
has
been
based
on
cultivable
surrogate
viruses.
[65,66
]
Diverse
range
of
fomites
can
become
contaminated
Both
high-touch
and
low-touch
surfaces
may
become
contaminated
by
both
fecal
matter
or
vomitus.
Food
(though
not
strictly
a
fomite)
may
become
contaminated
in
a
similar
way
by
infected
food
handlers.
[44

,46

,24,73,77]
Figure
2
Illustration
of
the
direct
and
indirect
transmission
potential
of
norovirus
over
time.
Infectiousness
Time
Direct transmission
Environmentally-mediated
transmission
Vomiting incident
Day 1
Days
One to two weeks
Current Opinion in Virology
At
it’s
peak,
we
hypothesize
that
direct
contact
is
the
highest
risk
of
transmission,
but
the
duration
of
infectiousness
from
environmental
contamination
is
likely
much
longer,
with
evidence
suggesting
two
weeks
or
longer
[48,52
].
Here,
this
concept
is
illustrated:
the
total
amount
of
transmission
resulting
from
direct
or
environmental
transmission
is
the
combined
area
under
each
curve.
The
average
infectious
period
from
direct
transmission
is
typically
just
over
1
day,
though
with
variable
duration
of
shedding
and
the
potential
for
environmental
transmission,
there
may
be
substantial
heterogeneity
in
the
infectious
period
among
cases.
We
do
not
intend
to
suggest
any
definitive
conclusions
of
the
overall
importance
of
direct
versus
environmental
transmission,
but
rather
to
illustrate
that
the
total
number
of
cases
resulting
from
a
single
case
(the
reproduction
number)
is
the
sum
of
the
area
under
two
curves
and
is
complicated
to
measure
in
practice.
Current
Opinion
in
Virology
2012,
2:96102
www.sciencedirect.com
Page 3
Author's personal copy
amount
of
detectable
virus
on
environmental
surfaces
[47

].
Anecdote
of
the
potential
of
fomites
to
harbor
and
transmit
virus
comes
from
an
observation
following
an
outbreak
in
a
UK
hospital.
Twelve
days
after
the
end
of
the
outbreak
and
following
standard
vacuum
cleaning,
two
workers
who
replaced
a
carpet
in
the
affected
unit
became
ill
with
norovirus
gastroenteritis
within
48
hours,
highlighting
the
environmental
stability
of
virus
[48].
Notably,
carpets
and
other
soft
furnishings
are
now
not
recommended
in
patient
care
areas
[43].
Detection
of
virus
in
the
environment
Human
noroviruses
cannot
be
grown
in
cell
culture
[49],
so
PCR
is
the
main
technique
for
detecting
norovirus
in
food,
water
and
environmental
samples.
However,
for
a
variety
of
reasons,
including
the
diversity
of
surfaces,
the
heterogenous
distribution
of
viral
contamination
and
the
possible
presence
of
PCR
inhibitors,
detection
in
food
and
environmental
samples
is
difficult
and
restricted
to
specialist
laboratories.
A
crucial
limitation
of
current
methods
is
that
they
detect
viral
RNA,
which
may
not
indicate
infectious
virus.
Thus,
results
from
environmen-
tal
samples
should
be
interpreted
with
caution
and
in
the
context
of
available
epidemiological
or
clinical
infor-
mation
[44

,50].
Sterile
swabs
can
be
used
for
environ-
mental
sampling,
after
which
viral
RNA
is
extracted
from
the
swabs;
testing
should
be
done
in
consultation
with
reference
laboratories
[51].
Norovirus
survival
and
persistence
For
viruses
that
are
transmitted
by
droplet
contamination
of
fomites,
survival
in
the
environment
may
play
a
key
role
in
transmissibility.
Virus
has
been
found
to
be
infec-
tious
to
human
volunteers
after
remaining
in
water
for
2
months;
intact
virus
capsid
can
be
detected
for
over
3
years
[52
].
But
since
noroviruses
cannot
be
cultured
in
vitro,
most
studies
that
have
been
performed
cannot
directly
examine
virus
survival
under
different
con-
ditions.
Feline
calicivirus
(FCV)
and
murine
norovirus
(MNV)
are
used
as
surrogates
for
norovirus,
with
the
latter
being
the
only
norovirus
that
can
be
grown
in
cell
culture
[53].
Both
surrogates
are
inactivated
by
relatively
extreme
UV,
heat,
and
high
pressure
[5456].
FCV
RNA
can
persist
on
experimentally
contaminated
surfaces
for
up
to
7
days
[57]
but
evidence
suggests
that
actual
survival
on
surfaces
is
substantially
shorter
(3
days)
[58].
The
clinical
and
epidemiological
implications
of
survival
characteristics
are
difficult
to
assess
directly,
though
the
laboratory
studies
cited
above
are
broadly
consistent
with
studies
of
norovirus
time-series
trends
and
associations
with
weather
variables.
Short-term
increases
in
norovirus
cases
have
been
associated
with
cool
and
dry
weather
in
England
and
Wales
and
Canada
[59,60].
However,
it
is
important
to
note
that
these
environmental
factors
inter-
act
with
host
factors
in
complex
ways.
The
emergence
of
novel
variants
that
escape
immunity
in
human
hosts
may
result
in
increased
incidence
during
warm
weather
months,
even
when
survival
conditions
are
unfavorable
[61].
For
seasonal
pathogens,
small
fluctuations
in
trans-
missibility
can
result
in
large
swings
in
incidence.
For
this
reason,
it
may
actually
be
impossible
to
conclusively
establish
the
underlying
environmental
causes
of
season-
ality
[62,63].
Role
of
disinfectants
and
sanitizers
Chemical
disinfection
is
a
central
approach
to
interrupt
the
chain
of
norovirus
transmission
[39,64].
The
EPA
main-
tains
a
list
of
approved
products
for
norovirus
disinfection
(http://www.epa.gov/oppad001/list_g_norovirus.pdf)
based
on
their
efficacy
against
FCV.
Notably,
FVC
exhibits
different
physiochemical
properties
than
human
norovirus
and
therefore
might
not
reflect
a
similar
disinfection
ef-
ficacy
profile.
MNV
may
in
some
ways
better
reflect
norovirus
susceptibility
(compared
with
FCV)
since
it
is
shed
in
feces
and
is
spread
by
the
fecal-oral
route,
although
it
does
not
cause
overt
gastroenteritis
in
mice.
Hence,
the
fact
that
FCV
is
less
resistant
to
disinfectants
than
MNV
may
suggest
that
norovirus
is
also
less
resistant
than
FCV
and,
therefore,
the
products
on
the
EPA
list
may
over-
estimate
the
efficacy
of
commercial
products
on
human
norovirus
[54,65].
Largely
due
to
the
uncertainty
from
in
vitro
studies,
CDC
recommends
chlorine
bleach
solution
at
a
concentration
of
10005000
ppm
(525
tablespoons
household
bleach
[5.25%]
per
gallon
of
water)
for
disinfection
of
hard,
nonporous,
environmental
surfaces
whenever
feasible
[33,66
].
In
healthcare
settings,
cleaning
products
and
disinfectants
used
should
be
EPA
registered
and
have
label
claims
for
use
in
health-care
settings
[33].
Hand
hygiene
is
also
a
key
part
of
the
environmental
trans-
mission
cycle
since
contaminated
hands
can
transfer
virus
to
touched
surfaces,
and
hands
may
be
a
vehicle
for
transferring
virus
from
contaminated
surfaces
back
to
humans
[36].
With
respect
to
the
efficacy
of
specific
hand
sanitizers,
in
vitro
studies
remain
inconclusive
for
the
same
reasons
as
for
chemical
surface
disinfection
(an
inability
to
culture
human
norovirus
and
unreliability
of
viral
RNA
as
an
indicator
of
infectious
particles).
The
use
of
alcohol-based
hand
sanitizers
remains
con-
troversial,
due
to
both
inconclusive
in
vitro
finger
pad
studies
[65,67,68]
and
epidemiological
studies
where
higher
outbreak
rates
have
been
detected
in
long-term
care
facilities
that
use
alcohol-based
hand
sanitizers
[69],
though
the
reason
for
association
in
this
one
study
are
debated
[70].
For
these
reasons,
washing
with
soap
and
running
water
for
at
least
20
s
remains
the
preferred
means
to
decontaminate
hands
[67,71].
Conclusion
Despite
increases
in
knowledge
about
norovirus
disease
and
transmission
in
recent
years,
we
have
yet
to
achieve
sufficient
understanding
of
the
role
of
environmental
Environmental
transmission
of
norovirus
gastroenteritis
Lopman
et
al.
99
www.sciencedirect.com
Current
Opinion
in
Virology
2012,
2:96102
Page 4
Author's personal copy
transmission
of
the
virus
and
what
impacts
on
disease
incidence
can
be
achieved
with
control
measures.
Current
evidence
suggests
that
the
virus
is
environmentally
stable
and
resistant
to
disinfection
and
that
environmental
con-
tamination
with
norovirus
is
common
both
within
and
outside
outbreak
settings.
Studies
confirming
the
import-
ance
of
environmental
transmission,
where
risk
of
disease
can
be
linked
to
exposure
to
a
contaminated
environ-
ment,
are
needed
to
firmly
establish
the
role
of
this
mechanism
of
spread,
especially
in
healthcare
settings.
Ultimately,
evidence
is
needed
for
effectiveness
of
con-
trol
measures
that
target
environmental
transmission.
References
and
recommended
reading
Papers
of
particular
interest,
published
within
the
period
of
review,
have
been
highlighted
as:
of
special
interest

of
outstanding
interest
1.
Patel
MM,
Widdowson
MA,
Glass
RI,
Akazawa
K,
Vinje
J,
Parashar
UD:
Systematic
literature
review
of
role
of
noroviruses
in
sporadic
gastroenteritis.
Emerg
Infect
Dis
2008,
14:1224-1231.
2.
de
Wit
MA,
Koopmans
MP,
Kortbeek
LM,
Wannet
WJ,
Vinje
J,
van
Leusden
F,
Bartelds
AI,
van
Duynhoven
YT:
Sensor,
a
population-
based
cohort
study
on
gastroenteritis
in
the
Netherlands:
incidence
and
etiology.
Am
J
Epidemiol
2001,
154:666-674.
3.
Phillips
G,
Tam
CC,
Conti
S,
Rodrigues
LC,
Brown
D,
Iturriza-
Gomara
M,
Gray
J,
Lopman
B:
Community
incidence
of
norovirus-associated
infectious
intestinal
disease
in
England:
improved
estimates
using
viral
load
for
norovirus
diagnosis.
Am
J
Epidemiol
2010,
171:1014-1022.
This
study
provides
the
most
robust
estimates
of
norovirus
disease,
based
on
a
community
cohort
in
England
where
diagnosis
was
performed
by
real
time
RT-PCR.
The
authors
develop
a
method
to
adjust
incidence
estimates
for
the
high
frequency
of
norovirus
detection
in
healthy
sub-
jects.
4.
Hall
AJ,
Rosenthal
M,
Gregoricus
N,
Greene
SA,
Ferguson
J,
Henao
OL,
Vinje
J,
Lopman
BA,
Parashar
UD,
Widdowson
MA:
Incidence
of
acute
gastroenteritis
and
role
of
norovirus,
georgia,
USA,
20042005.
Emerg
Infect
Dis
2011,
17:1381-1388.
5.
Karsten
C,
Baumgarte
S,
Friedrich
AW,
von
Eiff
C,
Becker
K,
Wosniok
W,
Ammon
A,
Bockemuhl
J,
Karch
H,
Huppertz
HI:
Incidence
and
risk
factors
for
community-acquired
acute
gastroenteritis
in
north-west
Germany
in
2004.
Eur
J
Clin
Microbiol
Infect
Dis
2009,
28:935-943.
6.
Scallan
E,
Hoekstra
RM,
Angulo
FJ,
Tauxe
RV,
Widdowson
MA,
Roy
SL,
Jones
JL,
Griffin
PM:
Foodborne
illness
acquired
in
the
United
States-major
pathogens.
Emerg
Infect
Dis
2011,
17:7-15.
7.
Lopman
BA,
Hall
AJ,
Curns
AT,
Parashar
UD:
Increasing
rates
of
gastroenteritis
hospital
discharges
in
US
adults
and
the
contribution
of
norovirus,
19962007.
Clin
Infect
Dis
2011,
52:466-474.
8.
Lindesmith
LC,
Donaldson
EF,
Lobue
AD,
Cannon
JL,
Zheng
DP,
Vinje
J,
Baric
RS:
Mechanisms
of
GII.4
norovirus
persistence
in
human
populations.
PLoS
Med
2008,
5:e31.
9.
Lopman
B,
Vennema
H,
Kohli
E,
Pothier
P,