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Lecture enteroviruses

Polio virus

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Lecture enteroviruses

  1. 1. ENTEROVIRUSES 2DWD • Enteroviruses are a genus of the picornavirus family which replicate mainly in the gut. • Single stranded naked RNA virus with icosahedral symmetry. • Unlike rhinoviruses, they are stable in acid pH. • Capsid has 60 copies each of 4 proteins, VP1, VP2, VP3 and VP4 arranged with icosahedral symmetry around a positive sense genome.
  2. 2. ENTEROVIRUSES 3DWD • At least 71 serotypes are known: divided into 5 groups – Polioviruses – Coxsackie A viruses – Coxsackie B viruses – Echoviruses – Enteroviruses (more recently, new enteroviruses subtype have been allocated sequential numbers (68-71))
  3. 3. ENTEROVIRUSES HISTORY 4DWD • Poliovirus - first identified in 1909 by inoculation of specimens into monkeys. The virus was first grown in cell culture in 1949 which became the basis for vaccines. • Coxsackieviruses - In 1948, a new group of agents were identified by inoculation into newborn mice from two children with paralytic disease. These agents were named Coxsackieviruses after the town in New York State. Coxsackieviruses A and B were identified on the basis of the histopathological changes they produced in Newborn mice and their capacity to grow in cell cultures. • Echoviruses - were later identified which produced cytopathic changes in cell culture and was nonpathogenic for newborn mice and subhuman primates. • More recently, new Enterovirus types have been allocated sequential numbers (68 - 71).
  4. 4. GENERA OF PICORNAVIRUSES 5DWD Enterovirus Poliovirus Coxsackie A and B Echo Other enteroviruses Diseases of the human (and other) alimentary tract (e.g. polio virus) Rhinovirus Disease of the nasopharyngeal region (e.g. common cold virus) Cardiovirus Murine encephalomyocarditis, Theiler's murine encephalomyelitis virus Aphthovirus Foot and mouth disease in cloven footed animals Hepatovirus Human hepatitis virus A Others Drosophila C virus, equine rhinoviruses, cricket paralysis virus
  5. 5. CATAGORIES OF ENTEROVIRUSES 6DWD VIRUS SEROTYPES CLINICAL DISEASES Polioviruses 3 types Asymptomatic infection, viral meningitis, paralytic disease, poliomyelitis Coxsackie A viruses 23 types ( A1-A22, A24) Viral meningitis plus, rash, ARD, myocarditis, orchitis Coxsackie B viruses 6 types (B1-B6) Viral meningitis, but no orchitis Echoviruses 32 types Viral meningitis, with orchitis Other Enteroviruses 4 types(68-71) Viral meningitis,
  6. 6. PROPERTIES OF ENTEROVIRUSES 7DWD PROPERTY ENTEROVIRUSES Size (nm) 22 – 30 Capsid Form Icosahedral Polypeptide VP1, VP2, VP3, VP4 RNA Type SS – PS RNA Molecular Weight 2000,000 – 2600,000 Acid Stable Optimal Temp.for growth (0 C) 370 C Density in Cesium chloride (g / m) 1 . 34
  7. 7. TRANSMISSION OF ENTEROVIRUSES 8DWD • Fecal – oral route: poor hygiene, dirty diapers( especially in day-care settings) • Ingestion via contaminated food and water • Contact with infected hands • Inhalation of infectious aerosols
  9. 9. Rhino,echo, coxsackie,polio Replication in oropharynx Primary viremia Target Tissue Secondary viremia Skin Muscle Brain Meninges Liver Echo Coxsackie A Echo Coxsackie A, B Polio Coxsackie Echo Polio Coxsackie Echo Coxsackie PATHOGENESIS OF ENTEROVIRUSES
  10. 10. POLIOMYELITIS 11DWD • Poliomyelitis (polio) is a highly infectious viral disease, which mainly affects young children. The virus is transmitted through contaminated food and water, and multiplies in the intestine, from where it can invade the nervous system.
  11. 11. POLIOMYELITIS 12DWD • Polio = gray matter, Myelitis = Inflammation of the spinal cord. • Involves CNS, produces serious Illness. • Causes Destruction of Motor Neurons in Spinal cord. • Produces FLACID PARALYSIS. • India has still has many cases of Poliomyelitis.
  12. 12. POLIO – AN ENTEROVIRUS 13DWD • Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae. Poliovirus is composed of a RNA genome and a protein capsid. The genome is single- stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is about 300 Angstrom in diameter with icosahedral symmetry.
  13. 13. CLASSIFICATION OF POLIOVIRUS 14DWD • Type 1 - Brunhilde and Mahoney. • Type 2- Lansing and MEFI. • Type 3- Leon and Salkett.
  14. 14. 15 CLASSIFICATION OF POLIOVIRUS DWD • Size is 27 nm • Contains 4 viral protein VP1 to VP 4 • VP1 Carries the major antigenic site, and combines with type specific neutralizing antibodies
  15. 15. PROPERTIES OF POLIOVIRUS 16DWD • Typical Entero virus. • Inactivated at 550 c for 30 mt. • Chlorine at 0.1 ppm • Ether is not effective. • Animal susceptibility. Monkey brain Requires Primate specific membranes. Contains 3 Antigenic types 1,2,3 Can be differentiated by ELISA and CF methods.
  16. 16. POLIO INFECTION 17DWD • Incubation 3 – 21 days • On average 14 days • Predisposing factors. Severe muscular activity can lead to paralysis, as it increases the blood flow May produce paralysis in the limb or bulbar region Injecting vaccines with adjuvant can predispose to paralysis Patients who underwent tonsillectomy have higher incidence as Ig G secretion is reduced Rarely oral Polio vaccine produces poliomyelitis.
  17. 17. PATHOLOGY & PATHOGENESIS 18DWD • Destroy the Anterior horn cells of the Spinal Cord • Do not Multiply in Muscles only muscles manifest with weakness and flaccid paralysis result is secondary. • Occasionally produce Myocarditis, Lymphatic hyperplasia.
  18. 18. PATHOLOGY & PATHOGENESIS 19DWD • Enter through Mouth, • Multiplies in Oropharynx tonsils and Intestines, • Excreted in Stool. • Enters the CNS from Blood. • Spread along the Axons of peripheral nerves to CNS. • Progress along the fibers of the lower motor neurons spinal cord or brain.
  19. 19. VIRUS INFECTION PROCESS 20DWD • The polio virus infects human cells by binding to an immunoglobulin-like receptor called CD155 (poliovirus receptor). • The exact mechanism that poliovirus uses for entering the cell is unknown. However, the interaction of poliovirus and CD155 causes a change in the shape of the viral particle that is needed to enter the cell • There are two thesis' for the way the viral nucleic acid to enters the cell. The first thesis is that the RNA of poliovirus is injected into the host cell through a pore in the membrane of the host cell. The second, and the one that is most likely and has the most support through research, is that the poliovirus is taken in by the host cell through endocytosis. • Poliovirus has ssRNA. Also known as single-strand RNA.
  20. 20. VIRUS INFECTION PROCESS 21DWD • The genome inside poliovirus can be used as mRNA and immediately translated by the host cell • Inside the host cell, the virus then takes over the cell’s translation machinery then causes inhibition of cellular protein synthesis. This favors the virus. • The poliovirus mRNA is then translated into a long polypeptide which is cleaved into 10 individual viral proteins • These proteins range from RNA polymerase to the proteins of the viral capsid • Translation of the viral RNA occurs by an IRES-mediated (internal ribosome entry site) mechanism • The IRES is the extremely long 5’ end of the poliovirus’ mRNA. • The assembly of viral particles is not fully understood. • The particles leave the host cell 4-6 hours after the initial infection. Each dying host cell can release 10,000 polio virions. • This means poliovirus is lytic
  22. 22. CLINICAL MANIFESTATIONS 23DWD • In apparent, Only 1% manifest with clinical features. • Can lead to permanent paralysis. • Incubation 7-14 days, ( 3-35 ) • May be abortive Poliomyelitis, Only Fever, Malaise, Drowsiness, Non paralytic Poliomyelitis, Aseptic Meningitis.
  23. 23. 24 0 20 40 60 80 100 Percent Asymptomatic Minor non-CNS illness Aseptic menigitis Paralytic
  24. 24. PARALYTIC POLIOMYELITIS 25DWD • Manifest as Flaccid Paralysis. ( Caused due to damage to Lower Motor Neurons.) • Partial recovery within 6 months. • Patient may continue with life time disability • Can involve Spinal cord, and Bulbo spinal region • Bulb spinal involvement can paralyze respiratory muscle and lead to Respiratory failure
  26. 26. ASEPTIC MENINGITIS 27DWD • Present with Non paralytic form with stiffness and pain in the back and neck region • Lasts for 2 -10 days • Recovery rapid and complete • On rare occasions advance to paralysis
  27. 27. LABORATORY DIAGNOSIS 28DWD • Viral isolation from Throat swabs, Rectal swabs. Stool specimens, • Transported in frozen containers. • Produce cytopathic effect on Human and Monkey cells • Produce cytopathic effects.
  28. 28. VIRAL ISOLATION 29DWD • From feces - present in 80% of cases in 1st week • In 50 % till 3rd week • In 25 % till several weeks • Collect the fecal sample at the earliest. • Primary monkey kidney is the ideal cell line for isolation of virus • Viral isolation must be interpreted with caution and clinical presentation
  29. 29. LABORATORY DIAGNOSIS (SEROLOGY) 30DWD • Estimation of Antibodies IgM • A paired sample is essential. • ELISA • CFT • Neutralisation.
  30. 30. IMMUNITY 31DWD • Permanent type specific. • 1 and 2 types have Heterotypic resistance. • Mother to Off spring immunity lasts for less than 6 months.
  31. 31. EPIDEMIOLOGY 32DWD • Endemic • Epidemic • Hygiene plays in spread of diseases. • Children < 5 in Developing countries.
  32. 32. PREVENTION & CONTROL 33DWD • Sabin’s Live attenuated vaccine • Grown in Monkey kidney cells, Human Diploid cells. Preserved at 40 C • Multiple doses are given • Given as oral Drops • At present only vaccine given in our National Programme of Immunization • Boosts Immunity with Production IgG ,IgM • And also IgA Participate as participant in Prevention.
  33. 33. VACCINATION SABIN'S- ORAL ADMINISTRATION 34DWD • Sabin’s vaccine is administered orally. • Contains Type 1 – 10 lakh, Type 2- 2 lakh Type 3- 3 Lakh. The virus are stable with Mg cl.
  34. 34. ORAL POLIO VACCINE ( SABIN’S) 35DWD • Highly effective in producing immunity to poliovirus • 50% immune after 1 dose • >95% immune after 3 doses • Immunity probably lifelong
  35. 35. ADVANTAGES OF LIVE VACCINE 36DWD • Induces long lasting immunity. • Induces local immunity in the form of IgA production ( gut immunity). • Administered orally, without the need of sterile syringes.
  36. 36. DISADVANTAGES OF LIVE VACCINE 37DWD • The only disadvantage of this vaccine is the vaccine strain particular type 3 strain can reverts to virulerence and cause paralysis in those who just been vaccinated. • It is estimated that vaccine induced poliomyelitis is seen in rate of 1 in 3000,000 vaccinations.
  37. 37. LIVE POLIO VACCINES –PROTECTS SOCIETY TOO 38DWD • The Live Polio vaccine infects multiples in the Intestines and thus Immunizes the Individual • Vaccines not only produces IgM and IgG in the blood but also IgA antibodies in the Intestines. • Which help the gut immunity
  38. 38. LIVE VACCINE ASSOCIATED POLIO 39DWD • On few occasions type 2 and type 3 virus may mutate in the course of multiplication • May lead to Vaccine associated Polio • But very negligible
  39. 39. INJECTABLE KILLED SALK VACCINE 40DWD • Salk Vaccine - A Killed Vaccine. (INACTIVATED) • Four Injections are administered in a period of two years, • Administration of periodic booster recommended. • Most of the Western Nations do use it.
  40. 40. VACCINATION IN IMMUNODEFICIENT 41DWD Only Killed viral vaccines used in Immunodeficient persons ( SALK )
  41. 41. PULSE POLIO IMMUNISATION 42DWD • The Indian Programme of PULSE POLIO Immunization is a part of it to eradicate Polio • Recent resurgence in UP and Bihar is a threat to the desired Goal. • In spite of best efforts thousands occur globally in Africa and Indian subcontinent.
  42. 42. DISEASES ASSOCIATED WITH COXASKIE A VIRUS 43DWD • Febrile illness with maculopapular rash. • Upper respiratory tract infection. • Paralytic disease. • Meningitis & encephalitis. • Peri and myocarditis. • Herpangina. • Hand, foot & mouth disease. • Acute hemorrhagic conjunctivitis.
  43. 43. DISEASES ASSOCIATED WITH COXASKIE A VIRUS 44DWD • Caused by group A Coxsackieviruses. • Characterized by fever, sore throat, pain on swallowing . • Small vesicles appear on the pharynx, Palate, uvula and tonsils . • Recovery is usual .
  44. 44. HAND FOOT & MOUTH DISEASE 45DWD • Caused by group A coxsackie viruses . • Small papules &vesicles develop on the buccal mucosa, hands and feet . • Recovery is usual .
  45. 45. DISEASES ASSOCIATED WITH COXASKIE B VIRUS 46DWD • Febrile illness with maculopapular rash. • Upper respiratory tract infection. • Paralytic disease. • Meningitis & encephalitis. • Peri & myocarditis. • Pleurodynia. • Juvenile diabetes/ pancreatitis .
  46. 46. PLEURODYNIA ( BORNHOLM DISEASE ). 47DWD • Caused by Coxsackie B viruses . • Characterized by fever, headache, severe stabbing chest pain, intensified by breathing and movement .
  47. 47. DISEASES ASSOCIATED WITH ECHO VIRUS 48DWD • Febrile illness with maculopapular rash. • Upper respiratory tract infection. • Paralytic disease. • Meningitis & encephalitis. • Peri & myocarditis.
  48. 48. DWD 49 Let us be partners in Eradication of Polio