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Dr.T.V.Rao MD
NOROVIRUSESAN EMERGING INFECTION
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Viruses infecting the gut
Viruses associated with gastroenteritis Rotaviruses Caliciviruses
Noroviruses Sapoviruses
Astroviruses adenoviruses 40, 41
Noroviruses
Sapoviruses
Rotaviruses
Astroviruses
Adenoviruses
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Viruses infecting the gut
Viruses associated with systemic infections enteroviruses parechoviruses
Viruses associated with infection in the
immunocompromised adenovirus types 42-48 cytomegalovirus human immunodeficiency virus
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Viruses infecting the gut
Presumptive enteric viruses
Torovirus
Coronavirus
Parvovirus
Picobirnavirus
Aichi virus
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NOROVIRUSES
Noroviruses (formerly Norwalk agent) is an RNA virus
(taxonomic family Caliciviridae) that causes
approximately 90% of epidemic non-bacterial outbreaks
of gastroenteritis around the world, and may beresponsible for 50% of all foodborne outbreaks of
gastroenteritis in the US. Noroviruses affects people of
all ages. The viruses are transmitted by faecally
contaminated food or water, by person-to-personcontact, and via aerosolization of the virus and
subsequent contamination of surfaces
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ABOUT NOROVIRUS
Norovirus Characteristics
Highly contagious
Multiple modes of transmission Stable in the environment
Resistant to routine disinfection methods
Carriers may not be symptomatic
Adapted from Strategies for Norovirus Infection Control Aboard Cruise Ships , Robert E. Wheeler, MD, 2003.
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NOROVIRUSWHAT'S IN A NAME?
The first norovirus strain, the Norwalk agent, was
discovered from an outbreak of gastroenteritis that
occurred in a school in Norwalk, Ohio, in 1968. Many
outbreaks with similar symptoms were later reportedfrom other settings, such as restaurants, nursing
homes, day care centers, and cruise ships.
Researchers found that these outbreaks were caused
by viruses that were related to the Norwalk agent, sothe viruses first became known as Norwalk-like viruses.
Norovirus is now the official name for this group of
viruses.DR.T.V.RAO MD 7
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Genetic Recombination
Requirements
co-infection of a single cell
relatedness of parental strains
Noroviruses
endemic co-circulation of genotypes
multiple infections associated with food and water borne spread environmental contamination and virus survival
faecal-oral route of transmission
limited heterotypic protection
absence of long term immunity
Mechanisms generating diversity among
noroviruses
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Neutral Networks: A model for NoV evolution
Method of representing random neutral drift between related proteins
Genotype populations that are linked by point mutation but are selectively neutral
Groups are defined by epitope structure, not sequence diversity
3 neutral networks
blue pre-2002 epidemic 2 clusters
orange 2002 epidemic 2006 7 clusters
yellow 2006 epidemic 4 clusters
Site A Site B 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
SHD N-N 1 10 3 v2 A 14
SHD S-N 1 2 v2 B 3
THD NSN 1 1 v1 C 2
THN NGT2 4
v2 D 6TRT STA 1 v1 E 1
TRT SST 1 1 v2 F 2
SRN STT 1 v6 G 1
TQN STT 10 4 2 v3 H 16
TQN NTT 9 v3 I 9
TQE STT 9 v2, v4 J 9
TQE NTT 1 v8 K 1
TQE SAT 1 v4 L 1
TQH STT 1 v3 M 1
n= 66
Number of
Strains
Motif Year S Domain
Variant*Epidemiological
Variant
pre-2002
2002epidemic
through to
2006
2006
epidemic
P2 Domain
ClusterSite A Site B 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
SHD N-N 1 10 3 v2 A 14
SHD S-N 1 2 v2 B 3
THD NSN 1 1 v1 C 2
THN NGT2 4
v2 D 6TRT STA 1 v1 E 1
TRT SST 1 1 v2 F 2
SRN STT 1 v6 G 1
TQN STT 10 4 2 v3 H 16
TQN NTT 9 v3 I 9
TQE STT 9 v2, v4 J 9
TQE NTT 1 v8 K 1
TQE SAT 1 v4 L 1
TQH STT 1 v3 M 1
n= 66
Number of
Strains
Motif Year S Domain
Variant*Epidemiological
Variant
pre-2002
2002epidemic
through to
2006
2006
epidemic
P2 Domain
ClusterSite A Site B 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
SHD N-N 1 10 3 v2 A 14
SHD S-N 1 2 v2 B 3
THD NSN 1 1 v1 C 2
THN NGT2 4
v2 D 6TRT STA 1 v1 E 1
TRT SST 1 1 v2 F 2
SRN STT 1 v6 G 1
TQN STT 10 4 2 v3 H 16
TQN NTT 9 v3 I 9
TQE STT 9 v2, v4 J 9
TQE NTT 1 v8 K 1
TQE SAT 1 v4 L 1
TQH STT 1 v3 M 1
n= 66
Number of
Strains
Motif Year S Domain
Variant*Epidemiological
Variant
pre-2002
2002epidemic
through to
2006
2006
epidemic
P2 Domain
ClusterSite A Site B 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
SHD N-N 1 10 3 v2 A 14
SHD S-N 1 2 v2 B 3
THD NSN 1 1 v1 C 2
THN NGT2 4
v2 D 6TRT STA 1 v1 E 1
TRT SST 1 1 v2 F 2
SRN STT 1 v6 G 1
TQN STT 10 4 2 v3 H 16
TQN NTT 9 v3 I 9
TQE STT 9 v2, v4 J 9
TQE NTT 1 v8 K 1
TQE SAT 1 v4 L 1
TQH STT 1 v3 M 1
n= 66
Number of
Strains
Motif Year S Domain
Variant*Epidemiological
Variant
pre-2002
2002epidemic
through to
2006
2006
epidemic
P2 Domain
Cluster
* as in Gallimore et al(2007)
Allen DJ et al. PLoS One, 2008DR.T.V.RAO MD 10
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Autum Winter Spring Summer Autum Winter Spring Summer
GII4 variant is selected, out of season outbreaks occur, becomes
epidemic
Normal winter season
Narrowing diversity:GII4 predominates
GII4 variants emerge
Return to normal season, wide diversity at the
beginning, narrowing as season progresses.
GII4 dominate and have an advantage over other co-circulating genotypes.
replicative advantage
greater transmissibility associated with a lower infectious dose
larger proportion of the population susceptible through inherited genetic factors,
better survival of the virus in the environment,
a mechanism that allows the virus to evade immune surveillance to some degree.
Autum Winter Spring Summer
Normal winter seasonNormal
summer
activity
Lack of short-term herd immunity to a new variant
Population protected in the short termagainst variant GII4
Population susceptible to other
genotypes due to short-term immune
protection.
Epidemic winter seasonUnusual
summer
activity
2002/03 epidemicStrain diversity
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Noroviruses
Family : Caliciviridae
Non-enveloped small round structuredviruses (27-32 nm diameter)
Genome: pos sense ssRNA ~ 7.5kb
Predominantly epidemic
The most common cause of outbreaks ofgastroenteritis
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Transmission Oral-fecal route
Food (39%)
Hands, person-to-person(12%)
Water (3%)
Also environmentalsurfaces: carpets, toilets,etc.
ABOUT NOROVIRUS
Adapted from Strategies for Norovirus Infection Control Aboard Cruise Ships , Robert E. Wheeler, MD, 2003.
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MANY SOURCES SPREAD
NOROVIRUSES
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Noroviruses are found in the stool and vomit of infected people.People can become infected by
Eating food or drinking liquids that are contaminated with
norovirus.
Touching surfaces or objects that are contaminated withnorovirus, and then placing their hand in their mouth.
Having direct contact with an infected person; for example, byexposure to the virus when caring for or when sharing food,drinks, or eating utensils with an infected person
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ABOUT NOROVIRUSModes of Transmission by Food
Food sources (i.e., food arrives contaminated)
Preparation
Food handlers
Customers
Most at risk: ready-to-eat foods that requirehandling but no subsequent cooking (e.g.,salads)
Adapted from Strategies for Norovirus Infection Control Aboard Cruise Ships , Robert E. Wheeler, MD, 2003.
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ABOUT NOROVIRUS
Norovirus Infection
Infectious dose of 10-100 virus particles
24-48 hour incubation period 12-60 hour duration of illness
A mild and short-lived illness
Treatment may indicate IV fluids
Viral shedding of 3 weeks or more
Adapted from Strategies for Norovirus Infection Control Aboard Cruise Ships , Robert E. Wheeler, MD, 2003.
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Outbreaks of noroviruses
infection often occur in closed or
semi-closed communities, such
as long-term care facilities,
overnight camps, hospitals,
prisons, dormitories, and cruiseships where the infection
spreads very rapidly either by
person-to-person transmission or
through contaminated food.Many
noroviruses outbreaks have beentraced to food that was handled
by one infected person
OUTBREAKS OF NOROVIRUSES
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OUTBREAKS RELATED TO NOROVIRUS AND
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OUTBREAKS RELATED TO NOROVIRUS AND
FOOD HANDLERS
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Outbreaks of Norovirus gastroenteritis have occurred in places where people haveconsumed water and/or food prepared or handled by others, including:
Restaurants
Cruise ships
Nursing homes
Hospitals
Schools
Banquet halls
Summer camps
Family dinners.
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After infection, immunity to
noroviruses is usually
incomplete and temporary.
There is an inherited
predisposition to infection,and individuals with blood
type O are more often
infected, while blood types
B and AB can confer partialprotection against
symptomatic infection.
PREDISPOSITION WITH NOROVIRUSES
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ABOUT NOROVIRUS
Norovirus Infection Symptoms Vomiting
Diarrhea
Nausea
Abdominal cramps
Headache, muscle aches
Fever (minority)
Dehydration
Up to 30% may be asymptomatic
Adapted from Strategies for Norovirus Infection Control Aboard Cruise Ships , Robert E. Wheeler, MD, 2003.
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USUAL SYMPTOMS WITH NOROVIRUS
INFECTION
Symptoms of Norovirus infection usually include
Diarrhea
Vomiting
Nausea
Stomach cramping Other, less common symptoms may include
Low-grade fever
Chills
Headache
Muscle aches
General sense of fatigue
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Severe dehydration can be
serious. The best way to prevent
dehydration is to drink plenty of
liquids. The most helpful fluids
for this purpose are oral
rehydration fluids. Other drinksthat do not contain caffeine or
alcohol can also help with mild
dehydration. However, these
drinks may not replace important
nutrients and minerals that arelost due to vomiting and diarrhea.
CAN CAUSE SEVER DEHYDRATION
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G O O S G OS S S C
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In special cases, for example,
when there is an outbreak of
gastroenteritis, there is a need to
identify Norovirus as the cause
of the illness. In these cases,
Norovirus can often be found instool samples of infected
persons by using special tests.
Sometimes, blood tests that
check for Norovirus antibodies
are also performed when thestool tests are inconclusive or
were not done. Food handlers
will often be asked for a stool
sample, or even a blood sample,
to help investigate the cause ofan outbreak.
MAKING A NOROVIRUS DIAGNOSIS IN SPECIAL
CASES
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DIAGNOSIS OF NOROVIRUSES
INFECTIONS
Diagnostic procedures for NV are based on the detection of virus instool samples by (immune) transmission electron microscopy (TEM),antigen ELISA, or polymerase chain reaction (PCR). In our study, atotal of 244 stool samples obtained from 227 patients between Marchand May 2002 were tested by TEM, antigen ELISA and in-house PCR.Our data showed that PCR has the highest sensitivity (94.1%),followed by TEM (58.3%), and ELISA (31.3%), while specificity washighest for TEM (98.0%), followed by ELISA (94.9%), and PCR(92.4%). All three methods tested (TEM, ELISA and PCR) are usefulfor epidemiological investigations in gastroenteritis outbreaks;however, to maximize diagnostic validity for individual cases, at leasttwo of the methods should be combined.
Ref Laboratory diagnosis of Norovirus: which method is the best?
Rameau HF, Strummer M Buxbaum S, Walczok A Preiser W Doerr HW.
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There is no vaccine to prevent
Norovirus infection, although this
is an area of active research.
There is no specific drug to
treat people with Norovirusillness.
Rehydration is important for
infected peoplethey must drink
plenty of liquids to replace fluid
lost through vomiting anddiarrhea. In some cases, fluid
may need to be given
intravenously.
NO SPECIFIC TREATMENT OR VACCINE FOR
NOROVIRUS INFECTION
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Practice proper hand hygiene:
Wash your hands carefully with
soap and water, especially after
using the toilet and changing
diapers and always before eating
or preparing food. Alcohol-basedhand sanitizers (containing at
least 62% ethanol) may be a
helpful addition to hand washing,
but they are not a substitute for
washing with soap and water.
PRACTICE PROPER HAND HYGIENE:
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Take care in the kitchen:
Carefully wash fruits and
vegetables, and cook oysters
and other shellfish thoroughly
before eating them.
Do not prepare food while
infected: People who are
infected with Norovirus should
not prepare food for others while
they have symptoms and for 3
days after they recover from their
illness.
OTHER MEASURES TO PREVENT
SPREAD
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OTHER MEASURES TO PREVENT
SPREAD
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Clean and disinfect contaminated surfaces:After an episode
of illness, such as vomiting or diarrhea, immediately clean and
disinfect contaminated surfaces by using a bleach-based
household cleaner as directed on the product label or a solution
made by adding 525 tablespoons of household bleach to 1gallon of water.
Wash laundry thoroughly: Immediately remove and wash
clothing or linens that may be contaminated with vomit or fecal
matter. Handle soiled items carefullywithout agitating themto avoid spreading virus. They should be laundered with
detergent at the maximum available cycle length and then
machine dried.
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Created by Dr.T.V.Rao MD for Medical and
Paramedical students in the Developing World
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