POLIOMYELITIS & PRION DISEASE Assist Prof Dr. Syed Yousaf Kazmi

LEARNING OBJECTIVES Discuss etiology, pathogenesis and epidemiology of poliomyelitis Explain the role of immunization on epidemiology of poliomyelitis List various prion diseases Discuss etiology, pathogenesis and transmission of Prion disease Discuss the role of sterilization & disinfection in transmission of prion disease

POLIOMYELITIS-ETIOLOGY Poliovirus causes Poliomyelitis Polio means “Grey”, Myelitis means “inflammation of spinal cord” Belongs to genus Enterovirus, Family Picornavirus Small (20–30 nm) nonenveloped Three serotypes 1,2 & 3: all three serotypes can produce same disease Serotype 1 severe disease

TRANSMISSION Fecal-oral route mainly Contaminated water or food Poliovirus survives in sewage water at low temperatures Multiplies in GIT of humans & passed in feces For each reported case of paralytic polio, around 200 to 3,000 other contagious asymptomatic carriers exist Humans are only natural host

EPIDEMIOLOGY In 1988, there were 388,000 cases of paralytic polio worldwide In 2005 there were fewer than 2000 1000 to 2000 cases each year In 2012 cases decreased to 223 Nearing eradication-But extremely difficult In three countries: Afghanistan, Nigeria, and Pakistan

POLIOMYELITIS-CURRENT STATUS

PATHOGENESIS Poliovirus infection results in asymptomatic virus shredders in 95% while 4% minor illness 1 % cases –Aseptic meningitis or Paralytic polio Incubation period 6-20 days Healthy non-immunized person ingest virus Virus multiplies in gut- lymphoid organs Viremia-Virus reach CNS Aseptic meningitis

PATHOGENESIS Risk factors for polio : Virus multiplies in motor neurons mainly in anterior horn cells Inflammatory cells cause death of motor neuron cells Affected nerves-paralysis Virus also affects brainstem-bulbar polio Lifelong immunity after infection IgA, IgG and IgM type antibodies Risk factors for polio : Immune deficiency, malnutrition, tonsillectomy, pregnancy

CLINICAL FEATURES Commonest presentation: asymptomatic (95%) Non specific : headache, sore throat, nausea Aseptic meningitis Paralytic polio: Asymmetric flaccid paralysis No sensory /cognitive loss Muscle disuse atrophy One leg/ one arm, or both legs/ both arms involved

ROLE OF IMMUNIZATION Two types of vaccines Inactivated Polio vaccine (Salk) Live attenuated vaccine (Sabin) Contain three serotypes PV1, PV2 & PV3 Both vaccines induce humoral antibodies, which neutralize virus entering the blood Four doses of IPV at 2, 4 & 6 to 18 months; upon entry to school at 4 to 6 years Booster adults on entering endemic county

ROLE OF IMMUNIZATION Direct role in disease prevention Western world has eradicated disease due to widespread immunization Only three countries with disease those that are war stricken Immunization campaign marred due to propagandas and un-education Low socioeconomic conditions further promote disease

INACTIVATED & ORAL POLIO VACCINES Killed (Salk) Live (Sabin) Attribute Yes Prevents disease No Interrupts transmission Induces humoral IgG Induces intestinal IgA Affords secondary protection by spread to others Interferes with replication of virulent virus in gut Yes (rarely) Reverts to virulence Can cause disease in the immunocompromised Injection Oral Route of administration Requires refrigeration Shorter Longer Duration of immunity

PRION DISEASE Prions are protein-containing particles with no detectable nucleic acid "Slow" infectious diseases Highly resistant infectious agent No inflammation or immune response in affected

PRION DISEASES-SPONGIFORM ENCEPHALOPATHY IP Host Agent Disease Months to years Humans, chimpanzees, monkeys Prion CJD: classical, familial, sporadic form Humans, cattle Variant CJDa Kuru DISEASES OF ANIMALS Sheep, goats, mice, hamsters Scrapie Cattle Bovine spongiform encephalopathy Months Mink, other animals Transmissible mink encephalopathy Mule deer, elk Chronic wasting disease

PRION DISEASES PATHOGENESIS BASIC CHARACTERISTICS OF ALL PRION DISEASES Transmissible spongiform encephalopathies Non conventional viruses Proteinaceous material without nucleic acid Diseases are confined to the nervous system Neuro-degeneration and spongiform changes Amyloid plaques may be present Long incubation periods (months to decades) Always fatal, no cases of remission or recovery

PRION DISEASES PATHOGENESIS Kuru & vCJD mainly spread by ingestion CJD also spread by blood transfusion Iatrogenically via corneal transplants, dura mater grafts, implanted brain electrodes, and growth hormone extracts made from human pituitary glands

PRION DISEASES PATHOGENESIS Infective material survive acid digestion Penetrate gut mucosa Prion Protein amplified in follicle dendritic cells in lymphatic tissue Prions then spread to the spleen Prions spread to CNS probably via the sympathetic nerves Normal PrPC to the infectious form (PrPSc)-pathology

PRION DISEASES CLINICAL FEATURES Relatively late in life Rapidly progressive dementia Behavioural disturbances Ataxia Death within one year No effect of antimicrobials Prion disease cerebrum

PRION DISEASES Resistant to proteolytic degradation Highly resistant to inactivation by heat, formaldehyde, and ultraviolet light Prions are resistant to the temperatures usually employed in cooking (imp in vCJD) Inactivated by protein- and lipid-disrupting agents such as phenol, ether, NaOH, and hypochlorite Instruments be sterilized using hypochlorite esp tonsillectomy instruments Autoclaving inactivates prion (121oC at 15 lb/in2 for 20 min)