Otho myx


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Otho myx

  1. 1. Orthomyxovirus<br />Paramyxoviruses<br />EDWARD-BENGIE L. MAGSOMBOL, MD<br />FPCP, FPCC, DASNC<br />Associate Professor, Department of Microbiology<br />Fatima College of Medicine<br />
  2. 2. A 22-year old man suddenly experienced headache, myalgia, malaise, dry cough, and fever. He basically felt “lousy”. After a couple of days, he had a sore throat, his cough had worsened, and he started to feel nauseated and vomited. Several of his family members had experienced similar symptoms during the previous two weeks.<br />
  3. 3. Characteristics:<br /><ul><li>Influenza A, B and C the only members
  4. 4. Enveloped virion; inactivated by detergents
  5. 5. Segmented negative-sense RNA genome with eight nucleocapsid segments
  6. 6. Genetic instability responsible for annual epidemics (mutation:drift) and periodic pandemics (reassortment: shift)</li></li></ul><li>Structure & Replication:<br /><ul><li>Envelope with two group-specific glycoproteins:</li></ul>Hemagglutinin (HA)<br /><ul><li>Functions:</li></ul>Viral attachment protein – bind to sialic acid on epithelial cell surface receptors<br />Promotes fusion of the envelope to the cell membrane<br />Hemagglutinates human, chicken and guinea pig rbc<br />Elicits protective neutralizing antibody response<br />
  7. 7. Structure & Replication:<br /><ul><li>Envelope with two group-specific glycoproteins:</li></ul>Neuraminidase (NA)<br /><ul><li>With enzyme activity
  8. 8. Cleaves the sialic acid on glycoproteins, including the cell receptor  prevents clumping & facilitates release of virus from infected cells
  9. 9. Target for two antiviral drugs: zanamivir (Relenza) and oseltamivir (Tamiflu)</li></li></ul><li>Structure & Replication:<br /><ul><li>Type-specific proteins: used to differentiate among influenza A, B, and C viruses</li></ul>Matrix protein (M1)<br /><ul><li>Viral structural protein
  10. 10. Interacts with nucleocapsid & envelope  promotes assembly</li></ul>Membrane protein (M2)<br /><ul><li>Forms membrane channel
  11. 11. Facilitates uncoating & HA production
  12. 12. Target for amantadine</li></ul>Nucleocapsid proteins (NP)<br />
  13. 13. Structure & Replication:<br /><ul><li>Transcribes and replicates its genome in the target cell nucleus
  14. 14. Assembles and buds from the plasma membrane</li></li></ul><li>Pathogenesis & Immunity:<br /><ul><li>Virus first targets & kills mucus-secreting, ciliated, and other epithelial cells  loss of primary defense system
  15. 15. Cleavage of sialic acid residues of mucus by NA  provide access to tissues
  16. 16. Preferential release of the virus at the apical surface of epithelial cells and into the lungs  promote cell-to-cell spread & transmission to other hosts</li></li></ul><li>Pathogenesis & Immunity:<br /><ul><li>Spread to lower respiratory tract  shedding of bronchial or alveolar epithelium
  17. 17. Promotes bacterial adhesion to the epithelial cells  pneumonia
  18. 18. Histologic: inflammatory response of mucosal membrane (primarily monocytes & lymphocytes) with submucosaledema</li></li></ul><li>Pathogenesis & Immunity:<br /><ul><li>Systemic symptoms due to the interferon and lymphokine response to the virus
  19. 19. Local symptoms due to epithelial cell damage
  20. 20. Interferon & CMI responses (NK & T cell) important for immune resolution and immunopathogenesis classic symptoms associated with interferon induction
  21. 21. Antibody important for future protection against infection </li></li></ul><li>Major contributors to pathogenesis<br />Antibody <br />Future protection<br />Immune response<br />T-cell response<br />Less frequent outcomes<br />Interferon induction<br />Desquamation of mucus-secreting and ciliated cells<br />Aerosol inoculation of virus<br />Replication in resp. tract<br />Influenza syndrome<br />Pneumonia <br />Secondary bacterial pneumonia<br />Primary viral pneumonia<br />CNS/muscle involvement<br />
  22. 22. Why is influenza difficult to control even when there is vaccination available?<br />
  23. 23. Antigenic Changes:<br />Antigenic drift<br /><ul><li>Minor change
  24. 24. Mutation of the HA and NA genes
  25. 25. Occurs every 2 to 3 years
  26. 26. Cause local outbreaks of influenza A & B</li></ul>Antigenic shift<br /><ul><li>Major change
  27. 27. Result from re-assortment of genomes among different strains, including animal strains
  28. 28. Associated with pandemics
  29. 29. Occurs only with influenza A</li></li></ul><li>Chicken influenza virus<br />Human influenza virus<br />Lung cell<br />Re-assortment of RNA genome segments<br />New strain of influenza virus<br />
  30. 30. How is the virus transmitted?<br />
  31. 31. <ul><li>Virus is spread by inhalation of aerosol droplets expelled during talking, breathing, and coughing.
  32. 32. Virus likes cool, less humid atmosphere
  33. 33. Virus is extensively spread by school children. </li></li></ul><li>Who is at risk?<br />
  34. 34. Seronegative people.<br />Adults: classic “flu” syndrome<br />Children: asymptomatic to severe respiratory<br /> tract infection<br />High-risk Groups:<br /><ul><li>Elderly
  35. 35. Immunocompromised people
  36. 36. People with underlying cardiac or respiratory problems (including people with asthma and smokers)</li></li></ul><li>What are the clinical syndromes associated with the virus? What are the possible complications?<br />
  37. 37. Diseases Associated with Influenza Virus Infections<br />
  38. 38. How would the diagnosis of influenza be confirmed?<br />
  39. 39. Laboratory Diagnosis of Influenza Virus Infection<br />
  40. 40. Which antiviral drugs are effective for the treatment of influenza virus infection? What are the targets & mechanisms of action of these drugs?<br />
  41. 41. Amantadine, Rimantadine<br /><ul><li>Target: M2 protein  inhibit an uncoating step
  42. 42. Do not affect influenza B or C virus</li></ul>Zanamivir (Relenza) & Oseltamivir (Tamiflu)<br /><ul><li>Target: neuraminidase  prevent release of virus from infected cells
  43. 43. Inhibit both influenza A and B
  44. 44. Effective for prophylaxis and for treatment during the first 24 to 48 hours after the onset of influenza A illness</li></li></ul><li>What is the best way to control the virus?<br />
  45. 45. The best way to control the virus is through IMMUNIZATION!<br /><ul><li>Killed vaccine representing the “strains of the year”
  46. 46. Killed (formalin-inactivated) whole-virus vaccine
  47. 47. Detergent-treated virion preparations and HA- and NA-containing detergent extracts of virus
  48. 48. Vaccination routinely recommended for the elderly and people with chronic pulmonary or heart disease.</li></li></ul><li>PARAMYXOVIRUSES<br />
  49. 49. Properties of Orthomyxoviruses and Paramyxoviruses<br />
  50. 50. Members of the Family Paramyxoviridae<br />
  51. 51. Members of the Family Paramyxoviridae<br />
  52. 52. Unique Features of the Paramyxoviridae<br /><ul><li>Large virion with helical nucleocapsid
  53. 53. Negative RNA genome
  54. 54. Envelope containing viral attachment protein (HN, paramyxovirus and mumps virus; H, measles virus, and G, RSV) and a fusion protein (F)
  55. 55. HN with hemagglutinin & neuraminidase activity
  56. 56. H with hemagglutinin activity
  57. 57. G without hemagglutinin or neuraminidase acvitity
  58. 58. Replicates in cytoplasm
  59. 59. Penetrate the cell by fusion with and exit by budding from the plasma membrane
  60. 60. Induce cell-to-cell fusion  multinucleated giant cells</li></li></ul><li>Envelope Spikes of Paramyxoviruses<br />1The measles and mumps fusion proteins are also hemolysins.<br />2In mumps and parainfluenza viruses, the hemagglutinin and neuraminidase are on the same spike and the fusion protein is on a different spike.<br />
  61. 61. An 18-year old college freshman complained of a cough, runny nose, and conjunctivitis. The physician in the campus health center noticed small white lesions inside the patient’s mouth. The next day, a confluent red rash covered his face and neck.<br />
  62. 62. <ul><li>How is the disease transmitted?
  63. 63. What clinical characteristics of this case were diagnostic for measles?
  64. 64. When was the patient contagious? </li></li></ul><li>
  65. 65. Transmission:<br /><ul><li>Inhalation of large-droplet aerosols</li></ul>Disease Mechanisms:<br /><ul><li>Infect epithelial cells of respiratory tract
  66. 66. Spread systemically in lymphocytes and by viremia
  67. 67. Replicate in cells of conjunctivae, respiratory tract, lymphatic system, blood vessels, and CNS
  68. 68. Characteristic rash caused by immune T cells targeted to measles-infected endothelial cells lining small blood vessels</li></li></ul><li>Mechanisms of spread and pathogenesis of measles<br />Local replication in respiratory tract<br />Inoculation of respiratory tract<br />Lymphatic spread<br />Viremia<br />Conjunctivae<br />Respiratory tract<br />Urinary tract<br />Small blood vessels<br />Lymphatic system<br />CNS<br />Virus-infected cell + immune T cells<br />Wide dissemination<br />RASH<br />Recovery (lifelong immunity)<br />Post-infectious encephalitis (immunopathological;etiology)<br />Subacutesclerosingpanencephalitis (defective measles virus infection of CNS)<br />No resolution of acute infection due to defective CMI (frequently fatal outcome)<br />
  69. 69. <ul><li>Incubation period: 7 to 13 days
  70. 70. Prodrome: high fever + 3C’s + P  most infectious
  71. 71. Koplik’s spots after 2 days of illness  last 24 to 48 hours
  72. 72. Appearance of exanthem within 12 to 24 hours of the appearance of Koplik’s spots
  73. 73. Rashes undergo brawny desquamation</li></li></ul><li>
  74. 74.
  75. 75. Clinical Consequences of Measles Virus Infection<br />
  76. 76. How can the infection be prevented?<br />
  77. 77. Post-exposure: Immune serum globulin given within six days of exposure<br />Pre-exposure:<br />Live, attenuated vaccine<br />MMR<br /><ul><li>Composition: </li></ul>Measles – Schwartz or Moratensubstrains of Edmonton B strain<br />Mumps – Jeryl Lynn strain<br />Rubella – RA/27-3 strain<br /><ul><li>Schedule: at 15-24 months and at 4-6 years
  78. 78. Efficacy: 95% lifelong immunization with a single dose</li></li></ul><li>A 13-month-old child had a runny nose, mild cough, and low-grade fever for several days. The cough got worse and sounded like “barking.” The child made a wheezing sound when agitated. The child appeared well except for the cough. A lateral radiograph of the neck showed a sub-glottic narrowing. <br />
  79. 79. What is the specific and common name for these symptoms?<br />
  80. 80. What other agents would cause a similar clinical presentation (differential diagnosis)?<br />What is the most common cause?<br />
  81. 81. How was the virus transmitted?<br />Answer: Droplet inhalation<br />
  82. 82. Parainfluenza Viruses<br />Characteristics:<br /><ul><li>Four serotypes
  83. 83. Infection limited to upper respiratory tract
  84. 84. Upper respiratory tract disease most common, but significant disease can occur with lower respiratory tract infection
  85. 85. Not systemic and do not cause viremia
  86. 86. Infection induces protective immunity of short duration</li></li></ul><li>Parainfluenza Viruses<br />Four serologic types<br /><ul><li>Types 1, 2, and 3
  87. 87. Second only to RSV as important causes of severe lower respiratory tract infection in infants and young children
  88. 88. Cause respiratory tract syndromes ranging from amild cold-like URTI to bronchiolitis to pneumonia
  89. 89. Especially associated with croup
  90. 90. Type 4
  91. 91. Mild upper respiratory tract infection in children and adults</li></li></ul><li>Parainfluenza Viruses<br /><ul><li>Clinical:
  92. 92. Main cause of croup in children < 5 y/o
  93. 93. Characterized by harsh cough (“seal bark cough” and hoarseness  due to subglottal swelling
  94. 94. Other clinical conditions: common cold, pharyngitis, otitis media, bronchitis, and pneumonia</li></li></ul><li>Respiratory Syncytial Virus<br /><ul><li>Most important cause of pneumonia and bronchiolitis in infants
  95. 95. Fusion protein causes formation of multinucleated giant cells  syncytia
  96. 96. Humans and chimpanzees are the natural hosts
  97. 97. Two serotypes – subgroup A and B</li></li></ul><li>Respiratory Syncytial Virus<br /><ul><li>MOT:</li></ul>Respiratory droplets<br />Direct contact of contaminated hands with the nose or mouth<br /><ul><li>Infection in infants more severe and usually involves lower respiratory tract than in older children and adults
  98. 98. No viremia occurs</li></li></ul><li>Respiratory Syncytial Virus<br /><ul><li>Severe disease in infants with immunopathogenic mechanism
  99. 99. Maternal antibody passed to infant  react with the virus  form immune complexes  damage respiratory tract cells
  100. 100. Most individuals with multiple infections  indicate incomplete immunity
  101. 101. IgA respiratory antibody reduces the frequency of infection as a person ages</li></li></ul><li>Respiratory Syncytial Virus<br /><ul><li>Clinical:</li></ul>Bronchiolitis<br />Pneumonia<br />Otitis media in young children<br />Croup <br />Upper respiratory tract infection similar to common cold in older children and adults<br />
  102. 102. Respiratory Syncytial Virus<br /><ul><li>Treatment:
  103. 103. Aerosolized ribavirin (Virazole) for severely ill hospitalized infants
  104. 104. Combination ribavirin + hyperimmune globulin may be more effective</li></li></ul><li>A 7 year-old boy developed fever, body malaise, and loss of appetite. This was followed by tender swelling around the right mandibular area, with increase in the pain everytime he drinks calamansi juice. The condition spontaneously resolved after one week.<br />
  105. 105. Mumps Virus<br /><ul><li>Two types of envelope spikes:</li></ul>With both hemagglutinin and neuraminidase activities <br />With cell-fusing and hemolytic activities<br /><ul><li>Only one serotype
  106. 106. Neutralizing antibodies directed against the hemagglutinin
  107. 107. Humans are natural hosts</li></li></ul><li>Mumps Virus<br /><ul><li>MOT: respiratory droplets
  108. 108. Infects both upper and lower respiratory tracts  spread through blood  parotid glands, testes, ovaries, pancreas, and in some cases, meninges
  109. 109. Occurs only once  subsequent cases may be caused by parainfluenza viruses, bacteria, and by duct stones</li></li></ul><li>Mumps Virus<br />
  110. 110. Mumps Virus<br />
  111. 111. Mumps Virus<br /><ul><li>Complications:</li></ul>Orchitis in post-pubertal males  may lead to sterility if bilateral<br />Meningitis – usually benign, self-limited, and without sequelae<br />
  112. 112. Mumps Virus<br /><ul><li>Prevention:</li></ul>Live, attenuated vaccine given subcutaneously to children at 15 months of age (MMR)<br />Immune globulin not useful for preventing or mitigating mumps orchitis.<br />
  113. 113. The End<br />