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Polio, Rotavirus, Rabies

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Title: Polio, Rotavirus, Rabies


1
Polio, Rotavirus, Rabies
  • MedCh 401
  • 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

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.

4
Polio Disease II
  • lt1 - 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
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
Polio Transmission
  • Fecal-oral
  • Oral-oral
  • Humans only known reservoir
  • Requires a receptor for cell attachment and entry

7
Christinas World, A. Wyeth, 1949
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

9
Polio vaccines
  • Inactivated Polio Virus - Salk
  • Live, oral, attenuated Polio Virus - Sabin

10
IPV v. OPV
  • Trivalent
  • Inactivated viruses
  • Highly effective vaccine
  • gt90 immune after 2 doses
  • gt99 immune after 3 doses
  • Duration unknown
  • Trivalent
  • Live, attenuated viruses
  • Highly effective vaccine
  • 50 immune after 1 dose
  • gt95 immune after 3 doses
  • Immunity probably lifelong

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 gt10 doses

12
IPV Vaccine Formulation
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

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 Labs IPV
  • 260 cases of type 1 polio, 192 paralytic
  • Due to incomplete inactivation of virus

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)

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

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

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

19
Rotavirus Transmission
  • Fecal-oral?
  • Improvements in water, sanitation, hygiene have
    not decreased incidence

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

21
Rotavirus Disease Burden
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

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

24
Rabies Pathogenesis
  • Acute viral encephalitis
  • 100 fatal
  • survivors are permanently brain damaged
  • Incubation period 5 days - several years
  • usually 20-60 days

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

26
Rabies Treatment
  • Immune globulin
  • Vaccine
  • No effective therapy once symptoms appear

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

28
Rabies Vaccines
29
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
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
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