1. 31May06KL Vadheim Lecture 81 Polio, Rotavirus, Rabies MedCh 401 Lecture 8

2. 31May06KL Vadheim Lecture 82 Polio Aka Poliomyelitis, Infantile paralysis 3 serotypes No cross-protection between serotypes Enteroviridae - Gastrointestinal disease Two types of virions –D particles; infective –C particles; non-infective

3. 31May06KL Vadheim Lecture 83 Polio Disease I ~95% - inapparent infections with no symptoms or only minor illness 4% - nonparalytic poliomyelitis; minor illness progresses to headache, vomiting, pain in limbs, back and neck; complete recovery.

4. 31May06KL Vadheim Lecture 84 Polio Disease II <1% - paralytic poliomyelitis –mild disease for several days –no symptoms for 1-3 days –rapid onset of flaccid paralysis with fever and progression to maximum extent of paralysis within a few days –paralysis of affected muscle is permanent –partial or total recovery of function within 6 months by compensation from unaffected muscle groups

5. 31May06KL Vadheim Lecture 85 Polio Disease III Post-polio Syndrome –late manifestation of acute paralytic polio –25-40% of people who had paralytic polio 15-40 years previously –muscle pain, exacerbation of existing weakness or new weakness/paralysis –failure of compensating muscle/nerves –NOT a consequence of persistent infection –NOT contagious

6. 31May06KL Vadheim Lecture 86 Polio Transmission Fecal-oral Oral-oral Humans only known reservoir Requires a receptor for cell attachment and entry

7. 31May06KL Vadheim Lecture 87 Christina’s World, A. Wyeth, 1949

8. 31May06KL Vadheim Lecture 88 U.S. Incidence, paralytic polio 1952 - peak incidence –21,000 cases 1980-1994 –127 cases 6 imported, wild poliovirus 2 indeterminate 119 Vaccine-associated paralytic polio (VAPP) 1995 –4 cases in unvaccinated Amish community

9. 31May06KL Vadheim Lecture 89 Polio vaccines Inactivated Polio Virus - Salk Live, oral, attenuated Polio Virus - Sabin

10. 31May06KL Vadheim Lecture 810 IPV v. OPV Trivalent Inactivated viruses Highly effective vaccine >90% immune after 2 doses >99% immune after 3 doses Duration unknown Trivalent Live, attenuated viruses Highly effective vaccine ~50% immune after 1 dose >95% immune after 3 doses Immunity probably lifelong

11. 31May06KL Vadheim Lecture 811 Polio vaccine schedules IPV - U.S., Europe, etc. –4 doses –2, 4, 6-18 months and 4-6 years IPV/OPV –four doses, any combination, by age 6 OPV, endemic countries –4 doses within first 12 months –epidemic/endemic areas: >10 doses

12. 31May06KL Vadheim Lecture 812 IPV Vaccine Formulation

13. 31May06KL Vadheim Lecture 813 IPV production VERO cells established on microcarriers with MEM and fetal calf serum Cells infected with Polioviruses types 1, 2 or 3, medium changed to serum-free M199 Viral suspensions clarified, filtered, concentrated Purification: anion exchange, gel filtration, anion exchange chromatography Adjust titers and inactivate at 37C, 12 days with formalin

14. 31May06KL Vadheim Lecture 814 Cutter Incident April, 1955 - Six manufacturers licensed to sell IPV Massive immunization of U.S. population initiated Cases of paralytic polio began to appear –All from Cutter Lab’s IPV –~260 cases of type 1 polio, 192 paralytic –Due to incomplete inactivation of virus

15. 31May06KL Vadheim Lecture 815 IPV v. OPV in U.S. 1955 - IPV licensed 1961 - Switched to OPV –superior ability to induce intestinal immunity –prevent polio spread among close contacts 1999 to present - IPV used exclusively –eliminates risk of Vaccine-Acquired Paralytic Polio (VAPP)

16. 31May06KL Vadheim Lecture 816 Polio eradication by 2000 Adopted in 1988 –350,000 cases paralytic polio/year –polio endemic in 125 countries 2003 status –784 confirmed cases –6 endemic countries 2005 status –61,606 cases paralytic polio –polio endemic in 4 countries

17. 31May06KL Vadheim Lecture 817 Rotavirus Reoviridae –segmented genome –prevalence of pathogenic serotypes varies worldwide –serotypes continually changing Heterotypic protection –natural infection or immunization with one serotype protected against another serotype

18. 31May06KL Vadheim Lecture 818 Rotavirus Pathogenesis Universal disease –All children are exposed and acquire antibodies by age 5 Leading cause of severe dehydrating diarrhea in infants and young children Sudden onset of watery diarrhea, fever and vomiting Recovery in 4-5 days

19. 31May06KL Vadheim Lecture 819 Rotavirus Transmission Fecal-oral? –Improvements in water, sanitation, hygiene have not decreased incidence

20. 31May06KL Vadheim Lecture 820 Rotavirus Incidence U.S. –500,000 physician visits –50,000 hospitalizations –20-40 deaths –Most common cause of severe diarrhea in children in areas with high living standards Developing world –~500,000 deaths in children –1,600 - 2,400 deaths per day

21. 31May06KL Vadheim Lecture 821 Rotavirus Disease Burden

22. 31May06KL Vadheim Lecture 822 Rotavirus vaccines Wyeth - Rotashield (Sept. 1998) –Live, oral, tetravalent –human/simian reassortant viruses –withdrawn in 1999 due to increased incidence of intussusception Merck - Rotateq (Feb. 2006) –Live, oral, pentavalent –Bovine/human reassortant viruses

23. 31May06KL Vadheim Lecture 823 Rotavirus vaccines GSK - Rotarix; not yet available in U.S. –Live, oral, attenuated, human –Monovalent –Cross-protective, replicates well in GI

24. 31May06KL Vadheim Lecture 824 Rabies Pathogenesis Acute viral encephalitis ~100% fatal –survivors are permanently brain damaged Incubation period 5 days - several years –usually 20-60 days

25. 31May06KL Vadheim Lecture 825 Rabies Transmission Saliva from bite of infected animal –Aerosol (bat caves) –Direct implantation (transplantation of infected tissue) Virus attaches to peripheral nerve endings and travels to the CNS Many wild animals serve as reservoirs –All mammals believed to be susceptible –Dogs, bats are primary carriers

26. 31May06KL Vadheim Lecture 826 Rabies Treatment Immune globulin Vaccine No effective therapy once symptoms appear

27. 31May06KL Vadheim Lecture 827 Rabies Vaccines Inactivated virus Human diploid cell vaccine (sanofi Pasteur) Purified Chick embryo culture vaccine (Chiron/Novartis)

28. 31May06KL Vadheim Lecture 828 Rabies Vaccines

29. 31May06KL Vadheim Lecture 829 Pre- v. Post-exposure Treatment 3 doses vaccine –days 0, 7, 21 or 28 Boosters –annual or biennial, depending on risk Rabies immune globulin –day 0 Vaccine –day 0, 3, 7, 14, 28 or 30 –IM in deltoid muscle –much less effective if injected into gluteal area

30. 31May06KL Vadheim Lecture 830 Rabies vaccine efficacy PCEC (Chiron) and HDCV (sanofi Pasteur) essentially equivalent No controlled clinical trials Vaccine + immune globulin –standard post-exposure treatment –100% effective IF timely administration adequate dose appropriate administration