Poliomyelitis

Pros and cons of polio vaccines- killed Salk vaccine(IPV)

Killed(salk,IPV) pros effective no reversion stable in transport and storage safe for immune deficient patients Cons no secretory IgA boosters required injection required no herd immunity does not prevent virus rep. in gut and hence further transmission expensive to produce

Poliovirus particle structure

enterovirus- member of the family of the picornaviridae -icosahedral- not a membrane virus -60 copies of each of the 4 capsid proteins- different pannels to create external shell -VP1 2 and 3- surface exposed VP4- internal positive sense RNA

Symptoms of polio

highly infectious viral disease enters body through the mouth and multiplies in the intestine-enterovirus can escapse and invade the nervous system and can cause total paralysis in a matter of hours initial symptoms are fever fatique headache, vomiting, stiffness in the neck and pain in the limbs one in 200 infections leads to irreversible paralysis among those paralysed 5-10% die when their breathing muscles become immobilised polio affect mainly children under 5

Polio- a disease of modern sanitation?

low endemic presence for centuries improved sanitation and increased population densities -more unprotected hosts -epidemic-0.5M/annum quarantine- closure of schools and pools faecal/oral contact route

Genome organisation and processing

positive sense RNA- mRNA like single polyprotein untranslated regions VPg protein- primer for transcription structural proteins -capsid non structural -enzymes/proteins for replication -3D polymerase -2A and 3C proteases

Pros and cons of vaccine: Live attenuated ( albert sabin, OPV)

pros effective lifelong immunity secretory immunity-IgA herd immunity easily administered inexpensive cons reversion-vaccine associated polio requires cold chain recombination unsafe for immunodeficient patients

Strategies for eradication

strong routine immunisation programe national immunisation days mopping up immunisation- vaccinating places that have been missed acute flaccid paralysis surveillance followed by -polio free certification laboratory containment of polio viruses conversion to use of inactivated vaccine stopping polio immunisation Switch to inactivated in UK- september 2004

Pathogeneis of polio

transmitted faecal orally multiplies locally at inital sites- tonsils- peyer patches or the the lymph nodes that drain these sites -virus shed in throat and faeces -may enter CNS by peripheral or cranial nerve axonal flow viraemia leads to virus replication in secondary sites high levels of virus replication in CNS destroys motor neurones leading to paralysis

Polio: control with vaccines

virus isolated in 1909 -can be made to infect non human primates -grow in cell culture Gamma globulin from recovered cases as cure; 1950;impractical Effective killed and live attenuated vaccines developed -jonas salk(inactivated:1955) -albert sabin(live oral;1962) World wide immunisationby 21st century?- polio vaccines work not quite tho...

Poliovirus vaccine

contains a mix of three serotypes- type 1,2 and 3 -antigenically distinct -no cross protection -inactivated polio vaccine-IPV grown in cell culture and formalin inactivated -developed by Jonas Salk Oral polio vaccine(OPV) -live attenuated -developed by albert sabin

Replication of polio

1. receptor mediated entry(CD155)-poliovirus receptor-PVR- cell surface receptor that polio binds to 2.uncoating 3.inhibition of cellular protein synthesis and translation(cap-binding protein) 4.polyprotein synthesis 5.co-translational processing 6.protein vesicle association 7.RNA vesicle association 8.negative strand synthesis 9.positive strand synthesis 10. more translation 11.capsid RNA association 12.packaging 13. cell lysis and virus release VIRUS GENOME REPLICATION OCCURS IN MEMBRANE VESICLE, not in the nucleus

Poliovirus replication in the gut

Dependent on gut microflora mice with high levels of microflora- virus replicates more readily than in mice with lower levels of microflora

Clinical and subclinical infection

Frank cases- minor illness in first 6/7 days and major illess from 10-15 days 1-2% Abortive cases minor illness-primary infection, no major illness 4-8% of cases Inapparent infection -assymptomatic, still infectious but no clinical signs -90-95% of cases virus can be present in faeces for up to 17 weeks even after infection has cleared antibody present neutralising-after 5 days- persists for lifetime complement fixing-after 8 days- perisists for 3-5 years

Iron lungs

Helped patients to breathe polio paralyses breathing muscles 10-20 million polio surviviors

Immune response to live attenuated and killed polio vaccine

OPV- causes infection in gut high IgA response -efficient -very protective, protects at gut level as well as systemically-lifelong IPV- not as efficient- safer

Polio vaccination: the balance of risk

Oral vaccine (Sabin) reversion can occur can revert back to paralytic form rare but can occur

Poliomyelitis clinical definition

Polio-grey myelitis- marrow pathology caused by destruction of grey matter of cns - motor neurones -paralysis -lower limb and thoracic An ancient disease -documented 4,000 years ago

eradication of polio: possible or difficult?

Possible: no animal vector or reservoir effective vaccine(s) virus survices poorly in the environment no chronic carrier state in healthy individuals difficult: can be asymptomatic 200:1 other diseases with similar symptoms reversion to virulence of vaccine recombination of vaccine and other enteroviruses society responses- don't get children vaccinated out of fear

Countries and polio

Uk is polio free syria- vaccine regime destroyed by warfare, spread to israel through water supply

Attenutation of polio virus

Virus put into monkey cells- many mutations occur no longer grows in human cells but can be used as a vaccine to protect against