Poliomyelitis Flashcards
what is poliomyelitis?
pathology caused by destruction of grey matter of CNS
- motor neurones
what does poliomyelitis cause?
paralysis of the lower limb and thoracic area
how many polio survivors are there worldwide?
10-20 million
what kind of disease is polio?
highly infectious viral disease
how does the polio virus enters the body?
through the mouth
where does the polio virus multiply?
in the intestine
what does the polio virus invade?
the nervous system
how long does it take for the polio virus to cause total paralysis?
a matter of hours
what are the initial symptoms of polio?
fever, headache, vomiting, stiffness in the neck and pain in the limbs
how may infections lead to irreversible paralysis (usually in the legs)
1 in 200
who does polio mainly infect?
children under five years of age
which are the effective polio vaccines developed?
- Jonas Salk - inactivated
- Albert Sabin - live oral
what has happened with polio in endemic countries?
polio-endemic countries have never stopped transmission of wild polio-virus
what happens in countries with re-established transmission?
have active and persistent poliovirus transmission more than 12 moths following an importation
what are countries with imported poliovirus experiencing?
ongoing outbreaks
what kind of virus is poliovirus?
enterovirus - member of the family Picornaviridae
what shape is poliovirus?
icosahedral
how many copies of each of 4 capsid proteins are there?
60
what are the four capsid proteins?
- VP1, 2, 3, (b-barrel structures - surface exposed
- VP4 - internal
what is the VPg protein?
a 22 a.a primer for transcription
what are the steps of replication of the poliovirus?
- receptor-mediated entry
- uncoating
- inhibition of cellular protein synthesis and translation (cap-binding protein)
- polyprotein synthesis
- co-translational processing
- protein-vesicle association
- RNA-vesicle association
- negative strand synthesis
- positive strand synthesis
- more translation
- capsid-RNA association
- packaging
- cell lysis and virus release
what is CD155?
poliovirus receptor (PVR)
where does the virus genome replication occur?
in a membrane vesicle, not the nucleus
how is poliovirus transmitted?
faecal-orally
where does the poliovirus multiply?
locally at initial sites (tonsils, Peyer’s Patches) or the lymph nodes that drain these sites
where is the virus shed?
in the throat and faeces
how can poliovirus enter the CNS?
by peripheral or cranial nerve axonal flow
what does viraemia lead to?
virus replication in secondary sites (muscle predominantly, but also lymph nodes and brown fat)
what gives the virus access to the CNS?
peripheral or cranial nerve retrograde axonal flow
what is the consequence of high levels of virus replication in the CNS?
destruction of motor neurones leading to paralysis (in approx. 0.5% infections)
what is the poliovirus replication in the gut dependent on?
on gut microflora
what do polio vaccines contain?
the 3 serotypes of poliovirus (type 1, 2, 3)
why is there no cross-protection in polio?
because the 3 serotypes are antigenic ally distinct
what is used to inactivate polio in the Inactivated polio vaccine (IPV)?
formalin
what type of vaccine is the oral polio vaccine (OPV)
live attenuated
what does the OPV give to the patient?
good secretory (IgA antibody) protection and long-lasting protection (lifelong)
what are the steps for attenuation of poliovirus?
- pathogenic virus is isolated from a patient and grown in human cultured cells
- the cultured virus is used to infect monkey cells
- the virus acquires many mutations that allow it to grow well in monkey cells
- the virus no longer grows well in human cells and may be a candidate for a vaccine
what are the advantages of the salk (killed) vaccine?
- effective
- no reversion
- stable in transport and storage
- safe for immune-deficient patients
what are the disadvantages of the salk (killed) vaccine?
- no secretory IgA
- boosters required
- injection required
- no herd immunity
- does not prevent virus replication in the gut and hence further transmission
- relatively expensive to produce
what are the advantages of the sabin (live attenuated) vaccine?
- effective
- lifelong immunity
- secretory immunity
- herd immunity
- easily administered
- inexpensive
what are the disadvantages of the sabin (live attenuated) vaccine?
- reversion - vaccine-associated paralytic poliomyelitis
- requires ‘cold chain’
- recombination
- unsafe for immunodeficient patients
why is it possible the eradication of poliomyelitis?
- no animal vector or reservoir
- effective vaccine(s)
- virus survives poorly in the environment
- no chronic carrier state in healthy individuals
why is difficult to eradicate poliomyelitis?
- unapparent infection 200:1
- other disease with similar symptoms
- reversion to virulence of vaccine (1 in 10^6 recipients)
- recombination of vaccine and other enteroviruses
- society responses
what are the strategies for eradication?
- strong routine immunisation programme
- acute flaccid paralysis (AFP) surveillance
- national immunisation days (NIDs)
- ‘mopping-up’ immunisation
what follows the strategies for eradication?
- polio-free certification
- laboratory containment of polioviruses
- conversion to use of inactivated vaccine
- stopping polio immunisation
how long does it take for a country to be declared polio-free?
2 years
in what two countries does polio remain endemic?
Pakistan and Afghanistan
