11-1-a-Viral Respiratory Tract Infections Part 2.txt

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11-1-a-Viral Respiratory Tract Infections Part 2.txt
2010-11-01 20:24:41

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  1. Viral Respiratory Tract Infections Part 2
    • Orthomyxoviruses: Influenza viruses A & B
    • Paramyxoviruses: Human parainfluenza viruses (HPIV) and Respiratory Syncytial Virus (RSV)
  2. Caracteristics of Orthomyxoviruses
    • Viral nucleid acid: RNA
    • Viral genome: single-stranded, non-segmented
    • Virion polymerase: present
    • Viral hemagglutinin (H) and neuraminidase (N): on SAME flycoptorein when present
    • Viral Cell fusion (F): on DIFFERENT glycoprotein than H and N
  3. Caracteristics of Paramyxoviruses
    • Viral nucleid acid: RNA
    • Viral genome: Single-stranded, segmented
    • Virion polymerase: present
    • Viral hemagglutinin (H) and neuraminidase (N): on DIFFERENT glycoproteins
    • Viral Cell fusion (F): on SAME flycoprotein as H.
  4. Influenza Viruses
    • Three serotypes: A, B, C
    • A and B cause serious illness (B in the middle)
    • B & C are more ancient in humans and seem to have reached some equilibrium with us
    • USA – 110, 000 Hospiralizations/yr
    • 36,000 deaths/yr
    • Highest rate: young children - >65 years of age people with medical conditions
  5. Influenza Virus Proteins
    • There are 8 genes encoding 10 proteins
    • Including an RNA > RNA polymerase and two surface glycoproteins: Hemagglutinin (H or HA) and neuraminidase (N or NA)
    • H and N determine the antigenic specificity of the virus
  6. Influenza H and N proteins
    • H glycoprotein: receptor-binding protein for the virus, recognizing a sialic acid (N-acetyl neuraminic acid) residue on the surface of a target cell
    • N glycoprotein: is a neuraminidase, that cleaves sialic acid. Its function is to cleave sialic acid residues (antagonistic to H!), but this is necessary to release virus effectively and not get it stuck to the cell that produced it.
  7. Influenza A: antigenic changes
    • Changes in H, N or both: ( there are 16 H and 9N subtypes but not all are associated with human infection and not all combinations have been noted)
    • Antigenic shift: major change
    • Antigenic drift: minor change
  8. Influenza virus mutations: Antigenic Drift
    • The normal process of mutation (change/insertion/deletion) of a nucleotide
    • Selection of the mutation will depend on its viability
    • Important mutations are those that are more fit and involve the H and N proteins
  9. Influenza virus mutations: Antigenic shift
    • A major change in the virus, where reassortment of the 8 genome segments takes place
    • When tso different strains are growing in one host.
    • If this involves the H or N protein, we get an antigenic shift (H1N1 to H2N1, for example)
    • Again selection depends on viability
  10. Influenza Transmission/Clinical Symptoms
    • Spread: cough/sneeze
    • Incubation period: 1-4 days
    • Replication site: Nasopharyngeal region
    • Symptoms: abrupt onset of fever, severe headache, muscle ache, extreme exhaustion
    • Symptoms are due to the immune response, not the virus growing in the muscles or joints!
  11. Influenza – additional clinical issues
    • Secondary bacterial pneumonia: is common following pulmonary influenza virus infections
    • Leads to a much worse prognosis!
    • High level of lung colonization by bacteria that are normally found in the nasopharynx
    • S. pneumonia, S. aureus, P. aeruginosa, H. influenzae: etc.
    • Part of any response to an influenza pandemic should be access to the appropriate antibotics (both antibacterial and antiviral)
  12. Influenza Dx
    • Suspected: on basis of a compatible illness when flu activity documented in community
    • Rapid Dx in clinical settings: detection of viral antigens (quicker) or PCR (more sensitive for RNA in cells from nasopharyngeal swabs
    • Lab Dx: 4-fold rise in antibody titer
  13. Influenza: Antiviral Agents Active against Influenza A ONLY:
    • Amantadine
    • Rimantadine
    • Work at early stages of viral replication (H3N2 strains are generally resistant)
    • Discovered serendipitously
  14. Influenza: Antiviral Agents Active against BOTH Influenza A and B
    • Neuraminidase inhibitors – prevent release of the virus from cells:
    • Zanamivir (relenza)
    • Oseltamivir (tamiflu)
  15. Influenza Vaccine 2010-11 (seasonal flu)
    • NOTE: flu vaccines mandatory for patient contact health care workers in NYS (2009). Not clear if this still applies in 2010
    • Inactivated (Trivalent Inactivated Vaccine): used for people over 50, immunocompromised and pregnant women.
    • Composition for 2010-11:
    • A/California/7/2009 (H1N1)-like
    • A/Perth/16/2009 (H3N2)-like
    • B/Brisbane/60/2008-like
    • Adults: > 50; health care workers; chronic disease patients; pregnant women, caregivers for <5 and > 50; immunosuppressed; nursing home residents
    • Children: 6mo-18yr; focus on <4 yr and chronic disease
  16. Influenza vaccine: Live attenuated (LAIV; FluMist)
    • Composed of temperature sensitive (ts) mutants
    • Only for HEALTHY people ages 2 TO 49 YEARS
    • Contraindicated for:
    • People with immune dysfunction
    • People with asthma
    • People on aspirin therapy and pregnant women
    • Seems to work better than TIV in kids, but perhaps not in adults
  18. Human parainfluenza viruses
    • HPIVs: common cause of respiratory tract disease in young children anc second only to RSV
    • Four serotypes: 1,2,3,4
    • Only 1-3 associated with disease
  19. Transmission of HPIVs
    • Transmitted: via the respiratory route
    • Incubation period = 1-7 days
    • Replication: nasopharyngeal region
  20. Clinical symptoms of HPIV
    • Cold-like syndrome; or URI
    • Symptoms: nasal congestion, sore throat and malaise
    • No viremia
  21. HPIV: Croup
    • More severe form of infection primarily in yong children (6 months-3 years)
    • HPIV-1 and HPIV-2 are associated with CROUP or laryngotracheobronchitis
    • Swelling of larynx and upper trachea
    • Spasmodic or “barking” cough
  22. HPIV: Bronchiolitis & Pneumonia
    • HPIV-3 is more often associated with bronchiolitis and pneumonian than other strains: .
    • Serious lower respiratory tract disease: especially in infants (<1 year of age)
    • Also elderly and immuno-compromised patients
  23. Immune Response to HPIVs
    • Duration of immunity (IgG) is transient:
    • Effective antibodies are against the two peplomers, HN and F on the envelope of the virus particle
  24. Dx of HPIV
    • Rapid diagnosis
    • Can be made by detection of viral-specific antigens in infected cells from nasal secretions by immunofluorescence
  25. Treatment of HPIVs
    • Conventional treatment: management of the patient, that is:
    • Hydration, maintenance of an adequate airway and therapy of associated bacterial infection, if relevant
    • NO specific aniviral agents or vaccine: .
  26. Respiratory Syncytial Virus
    • A leading cause of UPPER and/or LOWER respiratory tract illness among infants and children worldwide
    • Also causes mostly lower respiratory tract illness (LRTI) in older children and adults
    • In USA: 70,000-126,000 infants hospitalized / year
    • 14,000-62,000 elderly hospitalized / year
  27. Clinical symptoms of RSV
    • Spread: respiratory route
    • Incubation period:: 1 to 5 days
    • Virus replication: is mainly in the mucosal epithelium cells (nasopharyngeal)
    • No viremia: .
    • Virus carried to lower respiratory tract: Infants and young children (<6 months) develop bronchiolitis or pneumonia – often hospitalized with serious disease
  28. Rapid diagnosis or RSV
    Made by Detection of viral antigens in the cell of the nasal secretions using immnofluorescence (or PCR)
  29. RSV treatment
    • Conventional treatment: involves management of patient
    • Antiviral therapy: Ribavirin? (small clinical trial seemed promising, but in practice not very beneficial)
    • Passive immunization: for high-risk infants
    • RSV immune globulin intravenous (RSV-IGIV, also called RespiGam): recommended for children (<2yrs) with Chronic lung disorder (CLD) or premature birth
    • Palivizumab (Synagis): monoclonal antibody against the F glycoprotein of RSV- a highly conserved surface protein (also for the <2yo)