1. Norwalk Virus Phuong D. Nguyen

2. Introduction Family Caliciviridae Family Caliciviridae Small, nonenveloped RNA viruses Small, nonenveloped RNA viruses Distinctive Distinctive Cup-shaped depressions on a spherical capsid surface Cup-shaped depressions on a spherical capsid surface Size (27 to 35 nm) Size (27 to 35 nm) Genome encodes a single major polypeptide Genome encodes a single major polypeptide Cause of mucocutaneous and respiratory tract lesions in animals such as swine and cats Cause of mucocutaneous and respiratory tract lesions in animals such as swine and cats Norwalk virus is the best known of the human caliciviruses Norwalk virus is the best known of the human caliciviruses Humans are the only known hosts Humans are the only known hosts Has not been cultivated in vitro Has not been cultivated in vitro

3. Structure Small, round, 27 nm diameter, nonenveloped Amorphous surface (+) ssRNA, 7.5 kb Single structural protein, 60 kD

4. Clinical attributes Acute viral gastroenteritis Acute viral gastroenteritis Infectious dose Infectious dose Unknown Unknown Presumed to be low Presumed to be low Signs and symptoms Signs and symptoms Abdominal pain Abdominal pain Vomiting: non-bloody Vomiting: non-bloody Diarrhea: watery, non-bloody Diarrhea: watery, non-bloody Nausea Nausea Headache Headache Low-grade fever Low-grade fever Malaise Malaise Myalgia Myalgia Incubation period 24 to 48 hours Cases can occur within 12 hours of exposure Complications Dehydration among young and elderly Medical attention Recovery 24-60 hours Complete No long-term sequelae

5. Classification Norwalk and Norwalk-like viruses belong to the genus of Noroviruses and are named after location of outbreak Norwalk and Norwalk-like viruses belong to the genus of Noroviruses and are named after location of outbreak Norwalk, Ohio Norwalk, Ohio Snow Mountain, Colorado Snow Mountain, Colorado Taunton and Southampton, England Taunton and Southampton, England Otofuke and Sapporo, Japan Otofuke and Sapporo, Japan Sapovirus Sapovirus Formerly known as Sapporo-like virus Formerly known as Sapporo-like virus Genetic homology yet distinct antigenicity among Norwalk and Norwalk-like viruses by immune electron microscopy studies Genetic homology yet distinct antigenicity among Norwalk and Norwalk-like viruses by immune electron microscopy studies

6. History In 1968, 50% of 232 students and teachers at a Norwalk elementary school developed acute gastroenteritis In 1968, 50% of 232 students and teachers at a Norwalk elementary school developed acute gastroenteritis In 1972, the Norwalk virus was discovered by Dr. Al Kapikan from the National Institute of Allergy and Infectious Disease by immune EM of stool samples from the 1968 outbreak In 1972, the Norwalk virus was discovered by Dr. Al Kapikan from the National Institute of Allergy and Infectious Disease by immune EM of stool samples from the 1968 outbreak

7. Multiplication Current studies on the replication strategy of Norwalk virus Current studies on the replication strategy of Norwalk virus Cloning and sequencing of genome Cloning and sequencing of genome Three open reading frames comprise a single, positive strand of RNA Three open reading frames comprise a single, positive strand of RNA A single capsid protein is encoded by one of the reading frames A single capsid protein is encoded by one of the reading frames

8. Pathogenesis Fecal-oral route Eating contaminated food Raw shellfish Salad ingredients Drinking contaminated water Most common source Municipal to recreational Person to person Secondary transmission Direct contact

9. After ingestion, infection of the mucosa of the proximal small intestine, damage of microvilli, and malabsorption of D-xylose, lactose, and fat are caused by the virus After ingestion, infection of the mucosa of the proximal small intestine, damage of microvilli, and malabsorption of D-xylose, lactose, and fat are caused by the virus No invasion of the colon and thus, no fecal leukocytes in stool No invasion of the colon and thus, no fecal leukocytes in stool

10. Host defenses Most adults have serum antibodies Most adults have serum antibodies No protection against infection No protection against infection Markers or risk factors Markers or risk factors Studies have shown short-term immunity persisting for about 12 weeks Studies have shown short-term immunity persisting for about 12 weeks Strain-specific Strain-specific Repeated infections likely Repeated infections likely Further studies Further studies Genetic susceptibility Genetic susceptibility High risk of severe infection among those with O blood type High risk of severe infection among those with O blood type Repetitive past exposures Repetitive past exposures

11. Epidemiology 50% of all outbreaks involving acute infectious, nonbacterial gastroenteritis in the U.S. caused by the Norwalk virus 50% of all outbreaks involving acute infectious, nonbacterial gastroenteritis in the U.S. caused by the Norwalk virus Second most common cause of illness in U.S. after influenza Second most common cause of illness in U.S. after influenza Occurrence typically in older children and adults Occurrence typically in older children and adults Serum antibodies acquired during early adulthood Serum antibodies acquired during early adulthood Camps, schools, nursing homes, military populations, cruise ships Camps, schools, nursing homes, military populations, cruise ships Infection is worldwide based on seroprevalence studies Infection is worldwide based on seroprevalence studies Some evidence that Norwalk is spread by the respiratory route Some evidence that Norwalk is spread by the respiratory route Transmission through aerosolized virus-containing vomitus Transmission through aerosolized virus-containing vomitus Very rapid secondary spread of infection Very rapid secondary spread of infection

12. Diagnosis Virus identified in stool specimens Virus identified in stool specimens Antibodies measured in serum samples by immune EM or immunoassays Antibodies measured in serum samples by immune EM or immunoassays Few research laboratories with necessary reagents from human volunteer studies Few research laboratories with necessary reagents from human volunteer studies Limited diagnosis to community outbreak settings Limited diagnosis to community outbreak settings 27 state public health laboratories can test for virus in stool or contaminated food and water by reverse transcriptase polymerase chain reaction (RT-PCR) 27 state public health laboratories can test for virus in stool or contaminated food and water by reverse transcriptase polymerase chain reaction (RT-PCR)

13. Prevention Frequent hand-washing with soap and warm water Frequent hand-washing with soap and warm water After toilet visits After toilet visits After changing diapers After changing diapers Before eating or preparing food Before eating or preparing food Cook all shellfish thoroughly and wash fruits and vegetables Cook all shellfish thoroughly and wash fruits and vegetables Clean and disinfect contaminated surfaces Clean and disinfect contaminated surfaces Sanitary disposal of sewage Sanitary disposal of sewage No food preparation by persons infected during symptoms and 3 days after No food preparation by persons infected during symptoms and 3 days after

14. Control No specific antiviral therapy for Norwalk or Norwalk- like viruses No specific antiviral therapy for Norwalk or Norwalk- like viruses Long-lasting immunity by development of a vaccine not likely Long-lasting immunity by development of a vaccine not likely

15. Recent outbreaks September 2, 2003: 340 sick passengers and crew on a cruise ship Regal Princess docked in Manhattan September 2, 2003: 340 sick passengers and crew on a cruise ship Regal Princess docked in Manhattan July 7, 2003: 28 US Airways passengers coming back to North Carolina from an Arizona Indian reservation were ill before they boarded the plane July 7, 2003: 28 US Airways passengers coming back to North Carolina from an Arizona Indian reservation were ill before they boarded the plane December 4, 2002: 60 ill passengers aboard the Disney cruise ship Magic in Florida December 4, 2002: 60 ill passengers aboard the Disney cruise ship Magic in Florida November 28, 2002: ER at Toronto’s Sunnybrook Hospital closed November 28, 2002: ER at Toronto’s Sunnybrook Hospital closed March 13, 2002: 50% of 550 guests infected at an Oscar party March 13, 2002: 50% of 550 guests infected at an Oscar party

16. CDC’s vessel sanitation program 140 ships participate and given scores on a 100-point scale 140 ships participate and given scores on a 100-point scale A clean bill of health given to a score of 86 and over A clean bill of health given to a score of 86 and over 8 ships with a 100 point score 8 ships with a 100 point score Norwegian Star Norwegian Star Carnival Legend Carnival Legend Brilliance of the Seas Brilliance of the Seas Aurora Aurora Star Princess Star Princess Seven Seas Navigator Seven Seas Navigator The World The World Wind Surf Wind Surf