Norwalk VirusNorwalk Virus

Phuong D. NguyenPhuong D. Nguyen

IntroductionIntroduction Family CaliciviridaeFamily Caliciviridae

Small, nonenveloped RNA virusesSmall, nonenveloped RNA viruses Distinctive Distinctive

Cup-shaped depressions on a Cup-shaped depressions on a spherical capsid surfacespherical capsid surface

Size (27 to 35 nm)Size (27 to 35 nm) Genome encodes a single major Genome encodes a single major

polypeptidepolypeptide Cause of mucocutaneous and Cause of mucocutaneous and

respiratory tract lesions in respiratory tract lesions in animals such as swine and catsanimals such as swine and cats

Norwalk virus is the best Norwalk virus is the best known of the human known of the human calicivirusescaliciviruses Humans are the only known hostsHumans are the only known hosts Has not been cultivated Has not been cultivated in vitroin vitro

StructureStructure

Small, round, 27 nm diameter, nonenvelopedSmall, round, 27 nm diameter, nonenveloped Amorphous surfaceAmorphous surface (+) ssRNA, 7.5 kb(+) ssRNA, 7.5 kb Single structural protein, 60 kDSingle structural protein, 60 kD

Clinical attributesClinical attributes Acute viral Acute viral

gastroenteritisgastroenteritis Infectious doseInfectious dose

UnknownUnknown Presumed to be lowPresumed to be low

Signs and symptomsSigns and symptoms Abdominal painAbdominal pain Vomiting: non-bloodyVomiting: non-bloody Diarrhea: watery, non-Diarrhea: watery, non-

bloodybloody NauseaNausea HeadacheHeadache Low-grade feverLow-grade fever MalaiseMalaise MyalgiaMyalgia

Incubation periodIncubation period 24 to 48 hours24 to 48 hours Cases can occur within Cases can occur within

12 hours of exposure12 hours of exposure ComplicationsComplications

Dehydration among Dehydration among young and elderlyyoung and elderly

Medical attentionMedical attention RecoveryRecovery

24-60 hours24-60 hours CompleteComplete No long-term sequelaeNo long-term sequelae

Classification Classification Norwalk and Norwalk-like viruses belong Norwalk and Norwalk-like viruses belong

to the genus of Noroviruses and are to the genus of Noroviruses and are named after location of outbreaknamed after location of outbreak Norwalk, OhioNorwalk, Ohio Snow Mountain, ColoradoSnow Mountain, Colorado Taunton and Southampton, EnglandTaunton and Southampton, England Otofuke and Sapporo, JapanOtofuke and Sapporo, Japan

SapovirusSapovirus Formerly known as Sapporo-like virusFormerly known as Sapporo-like virus

Genetic homology yet distinct antigenicity Genetic homology yet distinct antigenicity among Norwalk and Norwalk-like viruses among Norwalk and Norwalk-like viruses by immune electron microscopy studiesby immune electron microscopy studies

HistoryHistory

In 1968, 50% of 232 students and teachers In 1968, 50% of 232 students and teachers at a Norwalk elementary school developed at a Norwalk elementary school developed acute gastroenteritis acute gastroenteritis

In 1972, the Norwalk virus was discovered In 1972, the Norwalk virus was discovered by Dr. Al Kapikan from the National by Dr. Al Kapikan from the National Institute of Allergy and Infectious Disease Institute of Allergy and Infectious Disease by immune EM of stool samples from the by immune EM of stool samples from the 1968 outbreak1968 outbreak

MultiplicationMultiplication

Current studies on the replication Current studies on the replication strategy of Norwalk virusstrategy of Norwalk virus

Cloning and sequencing of genomeCloning and sequencing of genome Three open reading frames comprise a Three open reading frames comprise a

single, positive strand of RNAsingle, positive strand of RNA A single capsid protein is encoded by A single capsid protein is encoded by

one of the reading framesone of the reading frames

PathogenesisPathogenesis

Fecal-oral routeFecal-oral route Eating contaminated foodEating contaminated food

Raw shellfishRaw shellfish Salad ingredientsSalad ingredients

Drinking contaminated waterDrinking contaminated water Most common sourceMost common source Municipal to recreationalMunicipal to recreational

Person to personPerson to person Secondary transmissionSecondary transmission Direct contactDirect contact

After ingestion, infection of the mucosa of After ingestion, infection of the mucosa of the proximal small intestine, damage of the proximal small intestine, damage of microvilli, and malabsorption of D-xylose, microvilli, and malabsorption of D-xylose, lactose, and fat are caused by the viruslactose, and fat are caused by the virus

No invasion of the colon and thus, no fecal No invasion of the colon and thus, no fecal leukocytes in stoolleukocytes in stool

Host defensesHost defenses Most adults have serum antibodiesMost adults have serum antibodies

No protection against infectionNo protection against infection Markers or risk factorsMarkers or risk factors Studies have shown short-term immunity Studies have shown short-term immunity

persisting for about 12 weekspersisting for about 12 weeks Strain-specificStrain-specific Repeated infections likelyRepeated infections likely

Further studiesFurther studies Genetic susceptibilityGenetic susceptibility

High risk of severe infection among those with O High risk of severe infection among those with O blood typeblood type

Repetitive past exposuresRepetitive past exposures

EpidemiologyEpidemiology 50% of all outbreaks involving acute infectious, 50% of all outbreaks involving acute infectious,

nonbacterial gastroenteritis in the U.S. caused by nonbacterial gastroenteritis in the U.S. caused by the Norwalk virusthe Norwalk virus

Second most common cause of illness in U.S. after Second most common cause of illness in U.S. after influenzainfluenza

Occurrence typically in older children and adultsOccurrence typically in older children and adults Serum antibodies acquired during early adulthoodSerum antibodies acquired during early adulthood Camps, schools, nursing homes, military populations, Camps, schools, nursing homes, military populations,

cruise shipscruise ships Infection is worldwide based on seroprevalence Infection is worldwide based on seroprevalence

studiesstudies Some evidence that Norwalk is spread by the Some evidence that Norwalk is spread by the

respiratory routerespiratory route Transmission through aerosolized virus-containing Transmission through aerosolized virus-containing

vomitusvomitus Very rapid secondary spread of infectionVery rapid secondary spread of infection

DiagnosisDiagnosis Virus identified in stool Virus identified in stool

specimensspecimens Antibodies measured in serum Antibodies measured in serum

samples by immune EM or samples by immune EM or immunoassaysimmunoassays

Few research laboratories with Few research laboratories with necessary reagents from human necessary reagents from human volunteer studiesvolunteer studies

Limited diagnosis to community Limited diagnosis to community outbreak settingsoutbreak settings

27 state public health 27 state public health laboratories can test for virus in laboratories can test for virus in stool or contaminated food and stool or contaminated food and water by reverse transcriptase water by reverse transcriptase polymerase chain reaction (RT-polymerase chain reaction (RT-PCR)PCR)

PreventionPrevention Frequent hand-washing with soap and warm Frequent hand-washing with soap and warm

waterwater After toilet visitsAfter toilet visits After changing diapersAfter changing diapers Before eating or preparing foodBefore eating or preparing food

Cook all shellfish thoroughly and wash fruits and Cook all shellfish thoroughly and wash fruits and vegetablesvegetables

Clean and disinfect contaminated surfacesClean and disinfect contaminated surfaces Sanitary disposal of sewageSanitary disposal of sewage No food preparation by persons infected during No food preparation by persons infected during

symptoms and 3 days aftersymptoms and 3 days after

ControlControl

No specific antiviral therapy for Norwalk No specific antiviral therapy for Norwalk or Norwalk-like virusesor Norwalk-like viruses

Long-lasting immunity by development of Long-lasting immunity by development of a vaccine not likelya vaccine not likely

Recent outbreaksRecent outbreaks September 2, 2003: 340 sick passengers and crew on September 2, 2003: 340 sick passengers and crew on

a cruise ship a cruise ship Regal PrincessRegal Princess docked in Manhattan docked in Manhattan July 7, 2003: 28 US Airways passengers coming back July 7, 2003: 28 US Airways passengers coming back

to North Carolina from an Arizona Indian reservation to North Carolina from an Arizona Indian reservation were ill before they boarded the planewere ill before they boarded the plane

December 4, 2002: 60 ill passengers aboard the December 4, 2002: 60 ill passengers aboard the Disney cruise ship Disney cruise ship MagicMagic in Florida in Florida

November 28, 2002: ER at Toronto’s Sunnybrook November 28, 2002: ER at Toronto’s Sunnybrook Hospital closedHospital closed

March 13, 2002: 50% of 550 guests infected at an March 13, 2002: 50% of 550 guests infected at an Oscar partyOscar party

CDC’s vessel sanitation CDC’s vessel sanitation programprogram

140 ships participate and given scores on 140 ships participate and given scores on a 100-point scalea 100-point scale

A clean bill of health given to a score of A clean bill of health given to a score of 86 and over86 and over

8 ships with a 100 point score8 ships with a 100 point score Norwegian StarNorwegian Star Carnival LegendCarnival Legend Brilliance of the SeasBrilliance of the Seas AuroraAurora Star PrincessStar Princess Seven Seas NavigatorSeven Seas Navigator The WorldThe World Wind SurfWind Surf