Otho myx
- 1. OrthomyxovirusParamyxovirusesEDWARD-BENGIE L. MAGSOMBOL, MDFPCP, FPCC, DASNCAssociate Professor, Department of MicrobiologyFatima College of Medicine
- 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.
- 3. Characteristics:Influenza A, B and C the only members
- 4. Enveloped virion; inactivated by detergents
- 5. Segmented negative-sense RNA genome with eight nucleocapsid segments
- 6. Genetic instability responsible for annual epidemics (mutation:drift) and periodic pandemics (reassortment: shift)Structure & Replication:Envelope with two group-specific glycoproteins:Hemagglutinin (HA)Functions:Viral attachment protein – bind to sialic acid on epithelial cell surface receptorsPromotes fusion of the envelope to the cell membraneHemagglutinates human, chicken and guinea pig rbcElicits protective neutralizing antibody response
- 7. Structure & Replication:Envelope with two group-specific glycoproteins:Neuraminidase (NA)With enzyme activity
- 8. Cleaves the sialic acid on glycoproteins, including the cell receptor prevents clumping & facilitates release of virus from infected cells
- 9. Target for two antiviral drugs: zanamivir (Relenza) and oseltamivir (Tamiflu)Structure & Replication:Type-specific proteins: used to differentiate among influenza A, B, and C virusesMatrix protein (M1)Viral structural protein
- 10. Interacts with nucleocapsid & envelope promotes assemblyMembrane protein (M2)Forms membrane channel
- 11. Facilitates uncoating & HA production
- 12. Target for amantadineNucleocapsid proteins (NP)
- 13. Structure & Replication:Transcribes and replicates its genome in the target cell nucleus
- 14. Assembles and buds from the plasma membranePathogenesis & Immunity:Virus first targets & kills mucus-secreting, ciliated, and other epithelial cells loss of primary defense system
- 15. Cleavage of sialic acid residues of mucus by NA provide access to tissues
- 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 hostsPathogenesis & Immunity:Spread to lower respiratory tract shedding of bronchial or alveolar epithelium
- 17. Promotes bacterial adhesion to the epithelial cells pneumonia
- 18. Histologic: inflammatory response of mucosal membrane (primarily monocytes & lymphocytes) with submucosaledemaPathogenesis & Immunity:Systemic symptoms due to the interferon and lymphokine response to the virus
- 19. Local symptoms due to epithelial cell damage
- 20. Interferon & CMI responses (NK & T cell) important for immune resolution and immunopathogenesis classic symptoms associated with interferon induction
- 21. Antibody important for future protection against infection Major contributors to pathogenesisAntibody Future protectionImmune responseT-cell responseLess frequent outcomesInterferon inductionDesquamation of mucus-secreting and ciliated cellsAerosol inoculation of virusReplication in resp. tractInfluenza syndromePneumonia Secondary bacterial pneumoniaPrimary viral pneumoniaCNS/muscle involvement
- 22. Why is influenza difficult to control even when there is vaccination available?
- 23. Antigenic Changes:Antigenic driftMinor change
- 24. Mutation of the HA and NA genes
- 25. Occurs every 2 to 3 years
- 26. Cause local outbreaks of influenza A & BAntigenic shiftMajor change
- 27. Result from re-assortment of genomes among different strains, including animal strains
- 29. Occurs only with influenza AChicken influenza virusHuman influenza virusLung cellRe-assortment of RNA genome segmentsNew strain of influenza virus
- 30. How is the virus transmitted?
- 31. Virus is spread by inhalation of aerosol droplets expelled during talking, breathing, and coughing.
- 32. Virus likes cool, less humid atmosphere
- 33. Virus is extensively spread by school children. Who is at risk?
- 34. Seronegative people.Adults: classic “flu” syndromeChildren: asymptomatic to severe respiratory tract infectionHigh-risk Groups:Elderly
- 36. People with underlying cardiac or respiratory problems (including people with asthma and smokers)What are the clinical syndromes associated with the virus? What are the possible complications?
- 37. Diseases Associated with Influenza Virus Infections
- 38. How would the diagnosis of influenza be confirmed?
- 39. Laboratory Diagnosis of Influenza Virus Infection
- 40. Which antiviral drugs are effective for the treatment of influenza virus infection? What are the targets & mechanisms of action of these drugs?
- 41. Amantadine, RimantadineTarget: M2 protein inhibit an uncoating step
- 42. Do not affect influenza B or C virusZanamivir (Relenza) & Oseltamivir (Tamiflu)Target: neuraminidase prevent release of virus from infected cells
- 43. Inhibit both influenza A and B
- 44. Effective for prophylaxis and for treatment during the first 24 to 48 hours after the onset of influenza A illnessWhat is the best way to control the virus?
- 45. The best way to control the virus is through IMMUNIZATION!Killed vaccine representing the “strains of the year”
- 46. Killed (formalin-inactivated) whole-virus vaccine
- 47. Detergent-treated virion preparations and HA- and NA-containing detergent extracts of virus
- 48. Vaccination routinely recommended for the elderly and people with chronic pulmonary or heart disease.PARAMYXOVIRUSES
- 49. Properties of Orthomyxoviruses and Paramyxoviruses
- 50. Members of the Family Paramyxoviridae
- 51. Members of the Family Paramyxoviridae
- 52. Unique Features of the ParamyxoviridaeLarge virion with helical nucleocapsid
- 54. Envelope containing viral attachment protein (HN, paramyxovirus and mumps virus; H, measles virus, and G, RSV) and a fusion protein (F)
- 55. HN with hemagglutinin & neuraminidase activity
- 56. H with hemagglutinin activity
- 57. G without hemagglutinin or neuraminidase acvitity
- 59. Penetrate the cell by fusion with and exit by budding from the plasma membrane
- 60. Induce cell-to-cell fusion multinucleated giant cellsEnvelope Spikes of Paramyxoviruses1The measles and mumps fusion proteins are also hemolysins.2In mumps and parainfluenza viruses, the hemagglutinin and neuraminidase are on the same spike and the fusion protein is on a different spike.
- 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.
- 62. How is the disease transmitted?
- 63. What clinical characteristics of this case were diagnostic for measles?
- 64. When was the patient contagious?
- 65. Transmission:Inhalation of large-droplet aerosolsDisease Mechanisms:Infect epithelial cells of respiratory tract
- 66. Spread systemically in lymphocytes and by viremia
- 67. Replicate in cells of conjunctivae, respiratory tract, lymphatic system, blood vessels, and CNS
- 68. Characteristic rash caused by immune T cells targeted to measles-infected endothelial cells lining small blood vesselsMechanisms of spread and pathogenesis of measlesLocal replication in respiratory tractInoculation of respiratory tractLymphatic spreadViremiaConjunctivaeRespiratory tractUrinary tractSmall blood vesselsLymphatic systemCNSVirus-infected cell + immune T cellsWide disseminationRASHRecovery (lifelong immunity)Post-infectious encephalitis (immunopathological;etiology)Subacutesclerosingpanencephalitis (defective measles virus infection of CNS)No resolution of acute infection due to defective CMI (frequently fatal outcome)
- 69. Incubation period: 7 to 13 days
- 70. Prodrome: high fever + 3C’s + P most infectious
- 71. Koplik’s spots after 2 days of illness last 24 to 48 hours
- 72. Appearance of exanthem within 12 to 24 hours of the appearance of Koplik’s spots
- 73. Rashes undergo brawny desquamation
- 75. Clinical Consequences of Measles Virus Infection
- 76. How can the infection be prevented?
- 77. Post-exposure: Immune serum globulin given within six days of exposurePre-exposure:Live, attenuated vaccineMMRComposition: Measles – Schwartz or Moratensubstrains of Edmonton B strainMumps – Jeryl Lynn strainRubella – RA/27-3 strainSchedule: at 15-24 months and at 4-6 years
- 78. Efficacy: 95% lifelong immunization with a single doseA 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.
- 79. What is the specific and common name for these symptoms?
- 80. What other agents would cause a similar clinical presentation (differential diagnosis)?What is the most common cause?
- 81. How was the virus transmitted?Answer: Droplet inhalation
- 83. Infection limited to upper respiratory tract
- 84. Upper respiratory tract disease most common, but significant disease can occur with lower respiratory tract infection
- 85. Not systemic and do not cause viremia
- 86. Infection induces protective immunity of short durationParainfluenza VirusesFour serologic typesTypes 1, 2, and 3
- 87. Second only to RSV as important causes of severe lower respiratory tract infection in infants and young children
- 88. Cause respiratory tract syndromes ranging from amild cold-like URTI to bronchiolitis to pneumonia
- 89. Especially associated with croup
- 90. Type 4
- 91. Mild upper respiratory tract infection in children and adultsParainfluenza VirusesClinical:
- 92. Main cause of croup in children < 5 y/o
- 93. Characterized by harsh cough (“seal bark cough” and hoarseness due to subglottal swelling
- 94. Other clinical conditions: common cold, pharyngitis, otitis media, bronchitis, and pneumoniaRespiratory Syncytial VirusMost important cause of pneumonia and bronchiolitis in infants
- 95. Fusion protein causes formation of multinucleated giant cells syncytia
- 96. Humans and chimpanzees are the natural hosts
- 97. Two serotypes – subgroup A and BRespiratory Syncytial VirusMOT:Respiratory dropletsDirect contact of contaminated hands with the nose or mouthInfection in infants more severe and usually involves lower respiratory tract than in older children and adults
- 98. No viremia occursRespiratory Syncytial VirusSevere disease in infants with immunopathogenic mechanism
- 99. Maternal antibody passed to infant react with the virus form immune complexes damage respiratory tract cells
- 100. Most individuals with multiple infections indicate incomplete immunity
- 101. IgA respiratory antibody reduces the frequency of infection as a person agesRespiratory Syncytial VirusClinical:BronchiolitisPneumoniaOtitis media in young childrenCroup Upper respiratory tract infection similar to common cold in older children and adults
- 103. Aerosolized ribavirin (Virazole) for severely ill hospitalized infants
- 104. Combination ribavirin + hyperimmune globulin may be more effectiveA 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.
- 105. Mumps VirusTwo types of envelope spikes:With both hemagglutinin and neuraminidase activities With cell-fusing and hemolytic activitiesOnly one serotype
- 106. Neutralizing antibodies directed against the hemagglutinin
- 107. Humans are natural hostsMumps VirusMOT: respiratory droplets
- 108. Infects both upper and lower respiratory tracts spread through blood parotid glands, testes, ovaries, pancreas, and in some cases, meninges
- 109. Occurs only once subsequent cases may be caused by parainfluenza viruses, bacteria, and by duct stonesMumps Virus
- 110. Mumps Virus
- 111. Mumps VirusComplications:Orchitis in post-pubertal males may lead to sterility if bilateralMeningitis – usually benign, self-limited, and without sequelae
- 112. Mumps VirusPrevention:Live, attenuated vaccine given subcutaneously to children at 15 months of age (MMR)Immune globulin not useful for preventing or mitigating mumps orchitis.
- 113. The End