Investigating Noroviruses: A Case Study

David Bergmire-Sweat, MPH North Carolina Department of Health and Human Services

Norovirus Facts

Small, round-structured viruses from Caliciviridae family

First recognized as pathogenic cause of gastroenteritis in 1968, Norwalk, Ohio

Transmitted via fecal-oral route Highly contagious—as few as 10 viral

particles can cause infection

Symptoms

Incubation period ~ 24-48 hours, can be less Vomiting Watery non-bloody diarrhea Abdominal cramps Nausea Low-grade fever Symptoms typically resolve ~ 24-60 hours (1-3

days)

Documented Modes of Transmission Foodhandler contamination of items in

restaurant Daycare centers Secondary person-to-person Aerosolized (vomiting and diarrhea) Cleaning up after ill person in a bathroom

Immunity & Epidemiology

Seems to be strain-specific and temporary (few months)

CDC estimates 23 million cases of acute gastroenteritis annually in U.S. due to noroviruses

CDC estimates noroviruses cause ~50% of all foodborne disease outbreaks

Detection

Best method is via reverse transcriptase polymerase chain reaction (RT-PCR)

Viral RNA Adults can shed viral particles for up to 2

weeks after symptoms resolve Infants and toddlers may shed longer

Case Study

Small state university north of Houston, TX

Student body ~ 10,000 students

2,054 students owned meal plans

125 students present to student health center and local hospital with gastrointenteritis in 24 hr period

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Symptoms

125 ill students on March 10-11 1998 23 admitted to hospital 91% reported vomiting 85% reported diarrhea (3+ loose stools in

24 hours) 68% reported abdominal cramps

Epidemic Curve

0

5

10

15

20

25

30

35

Date 5-Mar

6-Mar

7-Mar

8-Mar

9-Mar

10-Mar

11-Mar

12-Mar

13-Mar

14-Mar

15-Mar

Cases by Onset Date

Laboratory Investigation

62 stool samples sent to Texas Department of Health Lab in Austin

All negative for Salmonella, Shigella, Campylobacter, Yersinia, E. coli O157:H7, Bacillus cereus, and Staphylococcus aureus

18 samples tested for Norovirus by RT-PCR; 9 were positive

Challenges of Cafeteria Outbreaks Verifying Exposures Identifying potential

healthy controls Finding people to

interview them Hundreds of food

items Rule in/out other

exposures

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Rapid Action

Outbreak occurred toward end of week, right before Spring Break

Sanitarians from local health department investigated, realized cafeteria was about to close for week and perform massive cleaning/maintenance

Locked down all present food items, instructed staff not to throw anything out

Epidemiologic Investigation

Unmatched Case-control study by Texas Dept. of Health

36 ill subjects 136 well controls

Matched Case-control study by CDC

29 ill subjects 29 well controls

Findings – Matched Study Exposure Odds Ratio Confidence

Intervals P value

Deli sandwich 3/9 lunch

11.0 1.6-473 < 0.01

Deli sandwich 3/9 supper

6.0 0.7-276 0.06

Deli sandwich 3/10 lunch

8.0 1.1-355 0.02

Deli sandwich 3/10 supper

1.0 0.01-79 .75

Findings – Unmatched Study Exposure Odds Ratio Confidence

Intervals P value

Deli sandwich 3/9 lunch

11.1 3.9-32 < 0.001

Deli sandwich 3/9 supper

7.1 1.6-33

Interpretation

Both studies implicated deli sandwiches on 3/9 and 3/10

The more controls in a study, the better statistical power you have

No other restaurants or food items showed any association

Cafeteria Staff Investigation

Sanitarians and epidemiologists interviewed foodhandlers

All denied illness All except one submitted stool samples for

testing One refused; cafeteria manager fired her She was responsible for slicing deli meats

and making deli sandwiches

Discussion

CDC and TDH epidemiologists were disappointed with cafeteria manager decision to fire the one employee

Much more difficult to get cooperation Eventually did interview her She denied illness, but had infant with

diarrhea Stool sample from infant was PCR

positive for Norovirus

Chance to Learn Something

Researchers at Baylor College of Medicine agreed to try to find virus RNA on deli meat

Never been done before

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Success!

Lab successful in designing protocol for recovering virus RNA from deli meat

Pulsed-Field Gel analysis of PCR results showed identical pattern between infant, ill students, and deli meats

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Take Home Points

Viral gastroenteritis is easy to spread Foodhandlers must be extremely careful,

even when they are not sick, with hygiene It is possible to recover Norovirus from

food Quick reaction by local health department

sanitarians preserved food samples Collaboration with research lab advanced

science of food safety research

Investigating Noroviruses: A Case StudyNorovirus FactsSymptoms Documented Modes of TransmissionImmunity & EpidemiologyDetection Case StudySymptomsEpidemic CurveLaboratory InvestigationChallenges of Cafeteria OutbreaksRapid ActionEpidemiologic InvestigationFindings – Matched StudyFindings – Unmatched StudyInterpretationCafeteria Staff InvestigationDiscussionChance to Learn SomethingSuccess!Take Home Points