norovirus infections

8/3/2019 Norovirus Infections

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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 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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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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DR.T.V.RAO MD 8


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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


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 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

pre-2002

2002epidemic

through to

2006

2006

epidemic

P2 Domain


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


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 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

pre-2002

2002epidemic

through to

2006

2006

epidemic

P2 Domain


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


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 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

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



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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)



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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



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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



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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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DR.T.V.RAO MD 30

Created by Dr.T.V.Rao MD for Medical and

Paramedical students in the Developing World

Email

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norovirus infections

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