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Polio, Rotavirus, Rabies

Polio, Rotavirus, Rabies. MedCh 401 Lecture 8. 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. Polio Disease I.

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Polio, Rotavirus, Rabies

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  1. Polio, Rotavirus, Rabies MedCh 401 Lecture 8 KL Vadheim Lecture 8

  2. 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 KL Vadheim Lecture 8

  3. 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. KL Vadheim Lecture 8

  4. 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 KL Vadheim Lecture 8

  5. 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 KL Vadheim Lecture 8

  6. Polio Transmission • Fecal-oral • Oral-oral • Humans only known reservoir • Requires a receptor for cell attachment and entry KL Vadheim Lecture 8

  7. Christina’s World, A. Wyeth, 1949 KL Vadheim Lecture 8

  8. 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 KL Vadheim Lecture 8

  9. Polio vaccines • Inactivated Polio Virus - Salk • Live, oral, attenuated Polio Virus - Sabin KL Vadheim Lecture 8

  10. 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 IPV v. OPV KL Vadheim Lecture 8

  11. 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 KL Vadheim Lecture 8

  12. IPV Vaccine Formulation KL Vadheim Lecture 8

  13. 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 KL Vadheim Lecture 8

  14. 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 KL Vadheim Lecture 8

  15. 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) KL Vadheim Lecture 8

  16. 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 KL Vadheim Lecture 8

  17. 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 KL Vadheim Lecture 8

  18. 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 KL Vadheim Lecture 8

  19. Rotavirus Transmission • Fecal-oral? • Improvements in water, sanitation, hygiene have not decreased incidence KL Vadheim Lecture 8

  20. 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 KL Vadheim Lecture 8

  21. Rotavirus Disease Burden KL Vadheim Lecture 8

  22. 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 KL Vadheim Lecture 8

  23. Rotavirus vaccines • GSK - Rotarix; not yet available in U.S. • Live, oral, attenuated, human • Monovalent • Cross-protective, replicates well in GI KL Vadheim Lecture 8

  24. Rabies Pathogenesis • Acute viral encephalitis • ~100% fatal • survivors are permanently brain damaged • Incubation period 5 days - several years • usually 20-60 days KL Vadheim Lecture 8

  25. 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 KL Vadheim Lecture 8

  26. Rabies Treatment • Immune globulin • Vaccine • No effective therapy once symptoms appear KL Vadheim Lecture 8

  27. Rabies Vaccines • Inactivated virus • Human diploid cell vaccine (sanofi Pasteur) • Purified Chick embryo culture vaccine (Chiron/Novartis) KL Vadheim Lecture 8

  28. Rabies Vaccines KL Vadheim Lecture 8

  29. 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 Pre- v. Post-exposure Treatment KL Vadheim Lecture 8

  30. 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 KL Vadheim Lecture 8

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