1. 3. Gastrointestinal Route
Aka “alimentary” or “fecal-oral”
Viruses replicate in intestine
Spread to new hosts through contaminated food or water
Picornaviridae (most), Caliciviridae, Rotavirus

2. RNA Virus Families PICORNAVIRIDAE (Picorna Means Small RNA!!)
• Hundreds of species viruses are prevalent world-wide.
• cause many serious diseases of animals and man.
• Foot and mouth virus first animal virus described (1898).
• Poliovirus is an important model:
- first animal virus purified and crystallized.
- first inactivated vaccine used (Salk 1950’s).
- first picornavirus to be sequenced.
- first infectious cDNA clone of an animal virus.
- first picornavirus structure to be solved.

3. PICORNAVIRUS PROPERTIES
Capsids are small unenveloped nm icosahedra.
Many resistant to pH 3 to 9.
Plus sense single stranded RNA genomes (7400 bases).
Genome is monopartite.
RNA 5’ end has a covalently attached VPg (22-24 aa) and 3’ end is polyadenylated.
The 5’ end contains a highly structured (~740 nt) untranslated region that contains several AUG’s.
The naked RNA is sufficient for infection.
The RNA is translated into a polyprotein that is cleaved into Replication and Structural proteins.
All picornaviruses replicate in the cytoplasm.

4. 17 Genera as of 2011 Genus Enterovirus
- Poliovirus type member, 3 major types cause paralysis, now called enterovirus C
-Coxsackie viruses-now enterovirus A, B
-rhinoviruses
Genus Hepatovirus
- Hepatitis A, contagious liver infections.
Genus Cardiovirus
- EMC group, cause heart and brain inflammation
acid labile, source is a rodent reservoir.
Genus Apthovirus
- Foot and mouth disease, most destructive in Africa.

5. Evolutionary “tree”- how ancient are picornaviruses????

6. Hepatitis A Virus (HAV)

7. Hepatovirus and liver disease
Acute, self-limiting liver disease

8. Fecal-oral transmission of HAV
Hepatitis A Cases in Pennsylvania Rise to 510
Pittsburgh Blog « Green Onions Pulled From Chi-Chi's Menu Nationwide | Main | Pittsburgh Holiday Happenings »
November 17, 2003
Hepatitis A Cases in Pennsylvania Rise to 510 The number of confirmed Hepatis A cases in Western Pennsylvania have exceeded 500, including 3 deaths, in what has now become the largest hepatitis A outbreak in U.S. history, according to the Centers for Disease Control and Prevention. As a precaution, many restaurant chains are now removing green onions from their menus nationwide.
640 confirmed cases and 4 deaths
Traced back to onions from Mexico served in mild salsa during mid-October

9. General Features of Hepatitis A Infection
Enterically transmitted (fecal/oral route).
Multiplies in intestinal epithelial cells.
Moves into the bloodstream and reaches the liver.
After 15 to 50 days hepatitis symptoms appear.
Transient hepatitis last at most a few weeks.
Often referred to as “infectious hepatitis”.
Only a single serotype exists.
Vaccine available since 1992

10. HAV time course Virus ingested
Primary replication in intestinal lining?
Viremia
Virus shedding
Involvement of liver
Elevated enzyme profile
Immune response

11. Good ways to catch HAV
From 1 November 2012 to 30 April 2013, 15 confirmed cases of hepatitis A virus (HAV) infections with subgenotype IB and identical RNA sequence, and 89 probable cases, have been reported in 14 EU/EFTA countries. All cases have a travel history to Egypt.
Use of Molecular Epidemiology to Confirm a Multistate Outbreak of Hepatitis A Caused by Consumption of Oysters

12. The enterovirus formerly known as poliovirus
Humans only natural host
Long history in our species
Water-borne
Usually causes mild disease-often with no real symptoms
All enteroviruses are neurotropic

13. Disease progression Ingestion Primary replication, lymph nodes
Primary viremia
95% asymptomatic
Secondary viremia and further replication in other tissues
4-5% mild symptoms
Progression to CNS
Neurological symptoms-less than 1%are
Paralytic cases even more rare
Virus shedding in feces

14. A 20th Century Problem-Why?

15. Important findings leading to the Control of Poliovirus
Karl Landsteiner transmitted poliomyelitis from a boy to monkeys and suggested that the disease was caused by a virus.
1931- Sir Macfarlane Burnett found demonstrated seriologically distinct poliovirus strains. Infection with poliovirus was shown to be common but paralytic disease was rare. Three major strains were found to be responsible for paralysis.
John Enders found that poliovirus could be grown in cell cultures. Won the 1954 Nobel Prize.
Jonas Salk developed killed virus vaccines. By 1954, two million school children were vaccinated with % effectiveness. By 1958, nearly 450 million doses of vaccine had been given.
Albert Sabin developed a live oral vaccine. The virus replicates well in intestine and can be transmitted to others. In infants the virus is excreted in feces where it is transmitted to other family members who are protected.

17. Impact of vaccine Salk inactivated vaccine, injectable, 1955
Sabin attenuated vaccine, oral,
OPV provides strong immunity
“attenuated” vaccine

18. Eradication Initiative Begun 1988
WHO, UNICEF, CDC-goal: 2000
Rotary International
Private foundations
Strategy includes:
Childhood coverage
National Immunization Days
Surveillance
Follow up

19. Milestones Western Hemisphere polio-free 1994 Europe polio-free 2002
Pulse Polio campaign reduces cases in India to 66 by 2005; 1979 worldwide
India polio-free 2012
Endemic polio in 3 countries: Nigeria Pakistan Afghanistan
Scattered elsewhere-introduced

21. Learn in Business and Global Citizenship February 11, 2013 at 1:00 PM Bill Gates Says Expect Polio Eradication by 2018, Measles and Malaria, You're Next

22. Norwalk and Norwalk-like viruses (Noroviruses) Caliciviridae
School outbreak, Norwalk, Ohio, 1968
Acute gastroenteritis
50% of 232 students and teachers affected
Secondary attack rate of 32% among families
Virus particles discovered in stool filtrate, 1972

24. Norovirus outbreaks reported on 2 cruise ships that sailed the Caribbean
By Eliott C. McLaughlin, CNN
updated 4:50 PM EST, Fri January 31, 2014
Cruise passengers talk about Caribbean Princess trip that returned to Houston early
Friday, January 31, 2014

25. Disney ship docks with 195 ill
Next week's cruise canceled to sanitize vessel
Saturday, November 30, 2002 Posted: 12:32 PM EST (1732 GMT)
Passengers of Disney's cruise ship Magic arrive Saturday in Port Canaveral, Florida.
   
CNN's Susan Candiotti reports Disney announced it will cancel the next tour of the cruise ship Magic after confirming it is sailing with the Norwalk virus.
PORT CANAVERAL, Florida (CNN) -- Sunny skies greeted the Disney cruise ship Magic as it docked here early Saturday, carrying 195 sick passengers and crew members.
The vessel had completed a cruise of the western Caribbean, during which 172 passengers and 23 crew members came down with what is believed to be Norwalk virus.
U.S. Centers for Disease Control and Prevention (CDC) spokesman Owen Grant said the agency would decide by Monday whether stool samples collected from those complaining of gastrointestinal illness would be tested. If the culprit is confirmed to be Norwalk, it would be the second such outbreak on the cruise ship in as many weeks.