Update on Epidemiology and
Management of Norovirus
Aron J. Hall, DVM, MSPH
Viral Gastroenteritis Team
Centers for Disease Control and Prevention
ajhall@cdc.gov
Presented at American College Health Association Annual Meeting
Philadelphia, PA
June 3, 2010
“I have NO actual or potential conflict of interest in relation to this educational activity or presentation”
History
• 1929: “Winter vomiting disease” first described
• 1940s-1960s: 75% of gastroenteritis episodes of
unknown etiology
• 1968: Outbreak of acute gastroenteritis (AGE) at
elementary school in Norwalk, Ohio
• 1972: Viral particle seen by electron microscopy
• 1973-1992: Electron microscopy and serology used
to confirm outbreaks
• 1992-1994: Reverse transcription-polymerase chain
reaction (RT-PCR) developed
Disease Burden
• #1 cause of acute gastroenteritis in U.S.
– 23 million cases annually
– 1 in 13 Americans become ill each year
• Affects all ages, though greatest burden in
children and elderly
– 63,000 children hospitalized annually in U.S.
– 80 deaths annually among elderly in U.K.
• Occurs year round, though seasonal peak
activity during winter
• Found worldwide
Mead 1999 EID
Patel 2008 EID
Harris 2008 EID
Norovirus Detection in Outpatients,
British Infectious Intestinal Disease Study
Amar 2007 Eur J Clin Micro
Clinical Disease
• Incubation period: 12-48 hours
• Acute-onset vomiting and/or diarrhea
– Watery, non-bloody stools
– Abdominal cramps, nausea, low-grade fever
• Most recover after 12-72 hours
– Up to 10% seek medical attention; some require
hospitalization and fluid therapy
– More severe illness and death possible in elderly
and those with other illnesses
Laboratory Diagnostics
• No cell culture or animal model available
• Polymerase chain reaction (PCR)
– Gold standard: Quantitative real-time assay
– Conventional RT-PCR used for genetic sequencing
• Enzyme Immunoassays (EIA)
– Recent use of virus-like particles (VLP)
– Inadequate sensitivity (<50%) for clinical use
• Electron Microscopy (EM)
– Resource intensive
– Poor sensitivity
Viral Shedding
• Primarily in stool, but also vomitus
• Occurs for at least 2-3 weeks
• Peaks 4 days after exposure
– Greater in those with symptoms
– May occur after resolution of
symptoms
• Infectivity of shed virus unknown
• Infectious dose: 10-100 viral particles
Viral Shedding After
Experimental Infection
Asymptomatic
Vomiting and Diarrhea
Atmar 2008 EID
Immunity
• Short-term homologous immunity
• No persistent cross-protective immunity
• 30% infections asymptomatic
• Genetic susceptibility
– Histo-blood group antigens
– Secretor status (FUT2 gene)
Treatment
• No specific antiviral agents or vaccines
currently available
• Supportive care for dehydration,
primarily oral or IV fluid therapy
• Antibiotics, antiemetics, antimotility
agents generally not recommended
Transmission
• Person to person
– Direct fecal-oral
– Ingestion of aerosolized vomitus
– Indirect via fomites or contaminated environment
• Food
– Contamination by infected food handlers
– Point of service or source (raspberries, oysters)
• Recreational and Drinking Water
– Well contamination from septic tank
– Chlorination system breakdown
Norovirus Transmission Cycle
Intestinal Pathology
Symptomatic
(70%)
Asymptomatic
(30%)
A
B
Infected
Present
(40%)
Absent
(60%)
Protected
Susceptible to Infection
Viral Shedding
Stool
Vomit
Previously Acquired Immunity
Transmission Vehicles
Nonsecretor
(20%)
Innately
Resistant
Secretor
(80%)
Susceptible to infection
Exposed Population
Person-toPerson
Environment
& Fomites
Water
Food
Foodborne Burden
• Causes 67% of all foodborne illness in
U.S. from known agents
• Annual foodborne norovirus estimates
(rank among known agents)
– 9,200,000 cases of disease (#1)
– 20,000 hospitalizations (#1)
– 120 deaths (#4)
Mead 1999 EID
Confirmed and Suspected Etiology of 1270
Foodborne Outbreaks Reported to CDC, 2006
Other/Multiple
2%
Unknown
29%
Norovirus
40%
Chemical
5%
Parasites
1%
Bacteria
23%
CDC 2009 MMWR
Etiology of Foodborne
Outbreaks Reported to CDC
CDC 2009 MMWR
Single Food Commodities Involved
in Norovirus Outbreaks, 1998-2007
Outbreaks
Illnesses
Commodity
No. (%)
No. (%)
Leafy vegetables
124 (31.6)
3771 (33.7)
Fruits-nuts
58 (14.8)
2511 (22.4)
Mollusks
54 (13.8)
749 (6.7)
Poultry
40 (10.2)
645 (5.8)
Pork
26 (6.6)
564 (5.0)
Beef
23 (5.9)
369 (3.3)
Dairy
16 (4.1)
862 (7.7)
Grains-beans
13 (3.3)
157 (1.4)
Vine-stalk
11 (2.8)
447 (4.0)
392 (100)
11185 (100)
Total
Preliminary CDC Data
Norovirus Classification
• Genogroups
Broad
– >60% amino acid similarity
– 3 affect humans (GI, GII, GIV)
• Genotypes
– >80% amino acid similarity
– 8 GI genotypes, 17 GII genotypes
• Strains (variants, clusters)
– >95% amino acid similarity
– 11 GII.4 strains identified
Specific
Norovirus Classification Tree
Patel 2009 J Clin Virol
Norovirus GII.4 Pandemics
Winter Season
1995-96
2002-03
2004-05
2006-07
2006-07
2009-10
Strain Name(s)
Bristol (US95/96)
Farmington Hills (2002)
Hunter (2004)
Laurens (Yerseke, 2006a)
Minerva (Den Haag, 2006b)
New Orleans
GII.4 Strain Prevalence in
Outbreaks Tested at CDC
Siebenga 2009 JID
Setting of Norovirus Outbreaks
Reported to CDC, 1994-2006
250
GII-4
other GII
GI
200
150
100
50
0
Long-term Care
Restaurants,
Cruise Ships &
Facilities
Parties & Events
Vacations
Schools &
Communities
Zheng 2010 JCM
Seasonality of Norovirus Outbreaks
Reported to CDC, 1994-2006
Zheng 2010 JCM
Dynamics of Strain Evolution
and Population Immunity
500
Variant 1
450
Estimated population immunity
to circulating variant
400
Variant 2
350
300
250
200
Cases
150
100
50
0
2001
2002
2003
Challenges
•
•
•
•
•
Asymptomatic infections
Persistent in the environment
Resistant to common disinfectants
Very low infectious dose
Recurrent infections
College Campus Outbreaks:
Recent Examples
Outbreak 1:
California, 2008
• Large university (enrollment 32,000)
• Oct 3: Initial report of >30 students at emergency
dept or student health center (SHC) with AGE
• L.A. County Dept of Public Health (LACDPH)
– Conducted site visits for interviews with ill students
and environmental inspection
– Monitored daily GI reports from hospitals, SHC, and
residence hall advisors
• Campus administration sent mass email to all
students to complete web-based survey
– case ascertainment
– risk factor analysis
Outbreak 1:
Investigation Findings
• 5,227 (16%) students completed web-based survey
• 478 (1.5%) total cases identified via survey or
reported directly LACDPH
– 185 (39%) sought medical care at SHC
– 35 (7.3%) visited ED
– 10 (2.1%) hospitalized for dehydration
• 10 stool specimens tested
– 6 positive for norovirus GII by qRT-PCR
– All identical GII.6 Seacroft strain
• No single event, residence hall, eating venue, or ill
food handler were implicated
Student AGE Cases by Onset
Date, California, 2008
Outbreak 2:
Michigan, 2008
• Small college (enrollment 3,000)
• Nov 6: 60 AGE cases at campus medical clinic
• State and County health depts sent health alert
– local schools
– healthcare providers
– medical facilities
• Nov 7: total increased to 130 cases,
suggesting point source exposure
– One primary dining facility on campus
– Parents’ day activities began following day
Outbreak 2:
Actions Taken
• County health dept closed campus
– Curtail transmission and facilitate disinfection
– Only take-out and delivery available on campus
• Email & text messages sent to students
– Stay in residence unless required medical attention
– Completed electronic questionnaire if ill
– Disinfect dorm room with dilute bleach, wash soiled
linens and clothing, and wash hands frequently
• Ill faculty and staff advised to stay home until 72
hours after symptoms resolved
• Parents and media sent outbreak updates via
email and announcements on college website
Outbreak 2:
Investigation Findings
• 418 (13%) of 3,238 students ill
– 205 via electronic reporting
– 213 via direct reporting to medical clinic
• 33 (5.2%) of 630 faculty/staff ill
• 5 stool specimens tested
– All positive for norovirus GI by qRT-PCR
– All identical GI.4 strain
• 3 ill food service workers with vomiting
and diarrhea at work on Nov 4
Student/Faculty/Staff AGE Cases
by Onset Date, Michigan, 2008
Ill food
workers
Outbreak 3:
Wisconsin, 2008
• Large university (enrollment 42,000)
• Nov 6: 2 students from residence Hall A
(population 1,150) with AGE
– Students reported additional residents in
Hall A with similar symptoms
– AGE reported during following week from
other residence halls and a sorority house
Outbreak 3:
Actions Taken
• Campus health services led investigation
– Daily reports of ill residents from Hall A staff
– Email sent to all residence hall residents
(3,480) and fraternity/sorority members (2,700)
– If AGE during preceding 2 weeks, asked to
complete online questionnaire
• Students educated on hand washing
• Dormitories, public restrooms, communal
areas cleaned with approved disinfectants
Outbreak 3:
Investigation Findings
• 156 total student cases reported
– 138 identified online, 18 through campus health
– 36 (23%) sought healthcare, none hospitalized
– Symptoms included:
• diarrhea (92%)
• chills (80%),
• vomiting (88%) • body aches (81%),
• cramps (88%)
• subjective fever (65%)
– 93 cases among Hall A residents (8% attack rate)
• 5 stool specimens tested
– 2 positive for norovirus GII by qRT-PCR
– Sequencing not performed
Student AGE Cases by Residence
and Onset Date, Wisconsin, 2008
Index cases
reported
Email
sent
Outbreak Examples Summary
• 1,000 reported cases of illness, including at
least 10 hospitalizations
– Median outbreak duration: 19 days (range: 16-20)
– Minimum attack rates ranged from 1.5% to 12.9%
• College campuses at high risk for norovirus
outbreaks
– Extensive opportunities for transmission
– Numerous shared exposures and living areas
• Access to healthcare encourages illness
reporting and facilitates outbreak recognition
Prevention and Control
Recommendations
• Promote appropriate hand hygiene
– Wash with soap and water ≥ 20 seconds
– Alcohol-based hand sanitizers as adjunct
• Prompt and thorough environmental disinfection
– Bleach solution for contaminated surfaces (1000-5000 ppm)
– Other EPA-approved disinfectants?
• Exclude ill students/staff from food preparation for
≥48-72 hrs after symptom resolution
• Encourage ill students to seek medical care and limit
social activities
• Consider facility closure and/or event cancellation
• Disseminate recommendations promptly during
outbreak, including via electronic media
Acknowledgments
• University of Southern
California
• University of WisconsinMadison
– Craig Roberts
• Hope College
– Tom Renner
• Ottawa County Health Dept
– Paul Heidel
– Debra VandeBunte
• Los Angeles County Dept of
Public Health
– Curtis Croker
– Roshan Reporter
– Shikari Nakagawa-Ota
• Michigan Dept of Community
Health
– Brenda Brennan
• Wisconsin Div of Public
Health
– John Archer
Thank You… Questions?
Disclaimer: The findings and conclusions in this presentation are
those of the author and do not necessarily represent the views of
the Centers for Disease Control and Prevention.