virus WU.txt

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    • I. Common cold
    • a. Common causes- rhino-, corona-, adeno-
    • b. Less common causes- influenza, parainfluenza, enteroviruses
    • II. Sinusitis
    • III. Pharyngitis
    • IV. Laryngitis (Croup)
    • a. Common causes- parainfluenza
    • b. Less common causes- respiratory syncytial virus (RSV), other common cold viruses
    • I. Bronchitis
    • a. Common causes- parainfluenza
    • b. Less common causes- respiratory syncytial virus (RSV), influenza, common cold viruses
    • II. Bronchiolitis
    • a. Common causes- respiratory syncytial (RSV)
    • b. Less common causes- parainfluenza, influenza, adeno-
    • III. Pneumonia (affecting alveoli)
    • a. Common causes- respiratory syncytial virus (RSV), parainfluenza (<5 yrs old), influenza
    • b. Less common causes- adeno-
    • c. Mostly caused by bacteria
    • I. Sneezing, sore throat and runny nose w/ little fever
    • II. Leading cause of doctor visits
    • III. Up to 50% of acute respiratory infections in humans
    • 30-50%
    • a. 1st leading cause of the common cold
    • b. Picornaviruses
    • i. Non-enveloped
    • ii. Single stranded +RNA
    • c. Labile- sensitive to acid treatment
    • d. Limited to upper RT b/c optimal growth is 33 C (so 37 C is too warm in lower RT)
    • e. Transmission- aerosol and fomites (contaminated objects)
    • i. Frequent hand washing is recommended
    • f. NO vaccine
    • i. >100 types of rhinoviruses
    • ii. Antibody against one type will not protect from infection of another type
    • iii. No severe consequences so no incentive to develop a vaccine
    • g. NO anti-rhino drug
    • 10-30%
    • a. 2nd leading cause of the common cold (1/3 of cases)
    • b. Single stranded +RNA
    • c. Enveloped
    • d. SARS = severe acute respiratory syndrome (2003)
    • i. New syndrome in southern China in late 2002
    • ii. June 2003- 8,000 cases worldwide, 775 deaths
    • iii. Last outbreak was in 2004 from laboratory
    • iv. Shortage of masks during the outbreak
    • v. Origin of SARS
    • 1. 1/3 of original cases came from food handlers
    • 2. Closely related coronavirus was found in bats
    • a. Bats  palm civets  humans
    • b. Directly transmit to humans, evolves to facilitate human-to-human transmission
    • vi. quarantine is required for SARS and was effective
    • e. NO vaccine
    • f. NO anti-corona drugs
    • a. Double stranded DNA
    • b. Non-enveloped
    • c. First recognized among military recruits during 1950s (WWII)
    • d. >50 types
    • i. Type 1-7: acute respiratory illness
    • 1. Type 4, 7: military recruits
    • ii. Type 40, 41: gastroenteritis
    • e. Transmission- respiratory droplets and fecal matter
    • f. Most immunocompetent patients have full recovery
    • g. Most are asymptomatic
    • i. Most people have been infected w/ at least 1 type by age 15 (often unaware)
    • h. Vaccine (live attenuated adenoviruses) was used 1971-1990s but discontinued
    • i. Since 1999, 10-12% of recruits became infected
    • ii. Oral vaccine of type 4 and 7 in FDA approval review
    • i. NO anti-adeno drugs
    • j. May cause lower RT disease (bronchiolitis and pneumonia) much less commonly
    • I. Single stranded –RNA
    • II. Enveloped
    • III. Fusion protein (syncytia)
    • IV. Major cause of severe respiratory infection of infants/young children (<3 yrs old)
    • a. Croup (laryngotracheobronchitis)
    • b. Bronchiolitis
    • c. Pneumonia
    • a. Asymptomatic in most cases
    • b. Upper RT- mild cold-like symptoms older children and adults
    • c. Lower RT- severe complications in young children
    • d. 1st cause for croup (laryngotracheobronchitis)- upper or lower RT
    • e. NO antiviral drug
    • f. NO vaccine
    • a. Milder symptoms in older children and adults
    • b. 100,000 hospitalization/yr and 4,500 deaths/yr in USA
    • c. 1st cause for fatal respiratory tract infection in infants
    • d. Complications- 1st cause for infantile bronchiolitis/pneumonia
    • e. Diagnosis- rapid detection of RSV antigen from nasopharyngeal aspirates
    • f. Antiviral drugs- ribavirin = anti-viral RNA polymerase (used only in persons at high risk for the disease such as premature and immunocompromised infants)
    • g. Passive immunization- high risk groups
    • i. RespiGam- pooled human serum containing anti-RSV antibody
    • ii. Synagis- antibody against F (fusion) protein of RSV
    • I. Pandemic = new influenza virus, infects quickly, spreads worldwide in a short time (does NOT necessarily mean the consequences are severe)
    • a. (H2N2)- 1890
    • b. Spanish flu (H1N1)- 1918
    • i. 20-50 million deaths worldwide
    • ii. >500,000 deaths in USA)
    • iii. Recreated from frozen Alaskans  injected into mice who died w/in 6 days
    • c. Asian flu (H2N2)- 1957
    • i. 70,000 USA deaths
    • d. Hong Kong flu (H3N2)- 1968
    • i. 34,000 USA deaths
    • e. Russian flu (H1N1)- 1977
    • f. (H1N1)- 2009
    • i. <20,000 deaths
    • II. Segmented (8) –RNA
    • III. Enveloped
    • a. HA- attachment (hemagglutinin)
    • b. NA- virion release (neuraminidase)
    • c. M2- uncoating
    • IV. 3 types of influenza viruses
    • a. A- mammals and birds, most common/dangerous
    • b. B- mammals
    • c. C- mammals
    • V. Nomenclature- virus type, geographic origin, strain #, year of isolation, virus subtype (H#N#)
    • a. H = hemagglutinin (15 types)
    • b. N = neuraminidase (9 types)
    • VI. Life cycle of the influenza viruses
    • a. HA attaches to cell surface receptors  endocytosis into the cell
    • b. M2 uncoating via an ion channel into the vesicle to reduce the acidity
    • i. Amantadine drug prevents uncoating of virus
    • c. Virus enters the nucleus and RNA replication occurs in the nucleus
    • d. NA releases virus at the surface of the cell
    • i. Tamiflu drug prevents release of the virus
    • VII. Pathogenesis of influenza virus
    • a. Aerosol inoculation, replicate in RT
    • i.  antibody and T-cell responses for future protection
    • ii.  desquamation of mucus-secreting and ciliated cells
    • 1.  influenza syndrome
    • a. Fever
    • b. Sore throat
    • c. Cough
    • 2.  primary viral pneumonia
    • 3.  secondary bacterial infection  pneumonia
    • 4.  CNS and muscle involvement
  11. Complications of flu
    • a. ~36,000 deaths/yr in USA (highest risk in elderly >65 yrs)
    • b. Pneumonia is the major complication
    • i. Primary viral pneumonia
    • ii. Secondary bacterial pneumonia
    • iii. High risk groups- elderly, young children, immunocompromised patients (AIDS) and people w/ chronic medical conditions (DM)
    • c. Non-pulmonary complications
    • i. CNS involvement in young children
    • ii. Cardiac complications in elderly (myo/pericarditis)
    • IX. Anti-flu immunity
    • a. Flu-specific antibody
    • i. Anti-HA Ab binds to surface membrane of virus to prevent attachment and infection  creates future protection from the flu strain
    • b. Flu-specific cytotoxic lymphocytes
    • i. Kills the influenza-infected cells
    • c. If the virus evolves and develops a new viral HA then the old human antibody can no longer recognize it and infection may occur
  12. Antigen drift
    • a. Errors during RNA replication  minor changes in HA and NA
    • b. Pre-existing antibody does NOT work anymore
    • c. Outbreak of new viral strain occurs
    • d. Continuous process  vaccine strains must be updated annually at a minimum
  13. Antigen shift
    • a. Direct transmission of animal influenza A to humans (RARE)
    • b. Genetic reassortment (gene swapping, more COMMON method of infection)
    • i. Majority of genetic reassortment occurs in pigs (possibly triple reassortment)
    • ii. Some genetic reassortment can occur in humans
    • c. Major changes in HA and NA- totally different subtype, not just an amino acid change
    • d. Pandemics occur- new, spreading widely, NOT necessarily deadly
  14. Transmission (ecosystem of influenza A)
    • a. Natural reservoirs = birds (aquatic ducks) harbor all types of influenza viruses
    • b. Transmit viruses to domestic birds/pigs/horses
    • c. Transmit viruses to humans
  15. Vaccine for influenza
    • a. Killed- grown in eggs; Ab only
    • i. Short-lived protective effects
    • ii. Need to decide which strain to use by February
    • iii. More commonly used
    • b. Live attenuated- cold adapted, grown in eggs; Ab + CTL (cytotoxic lymphocytes)
    • i. Limited in upper tract
    • ii. Flumist (nasal spray)
    • iii. Mucosal immunity
    • iv. Only to healthy individuals
  16. Anti-influenza drugs- FDA approved antiviral drugs against influenza (target M2 or NA)
    • a. Amantadine… Oral… M2 (uncoating)… A
    • b. Rimantadine… Oral… M2 (uncoating)… A
    • c. Oseltamivir/Tamiflu… Oral… NA (budding)… A/B
    • d. Zanamivir/Relenz… inhalation… NA(budding)… A/B
    • *High proportion of influenza in USA is resistant to amantadine/rimantadine  do NOT use
  17. Avian influenza
    • a. Most deadly subtypes for birds are H5 and H7
    • b. 1997, H5N1 virus isolated in chickens farms of Hong Kong, killed 70-100% of infected chickens
    • c. 1st isolation of H5N1 in humans had 6/18 confirmed deaths
    • i. Exposure to infected poultry, feces or dust/soil contaminated
    • ii. H5N1 does NOT infect humans easily
    • iii. Rare human-to-human transmission (avian version of HA)
    • d. 1999, 1st isolation of avian H9N2 in humans
    • i. Contact w/ sick or dead poultry
    • ii. Children and young adults
    • iii. Rare human-to-human transmission
    • iv. Indonesia > Vietnam > China > Thailand > Turkey > Cambodia > Iraq
    • e. Concerns of avian flu
    • i. Genetic reassortment btwn H5N1 and human viruses  easier transmission
    • ii. Little immunity to H5 N1 in the population
  18. Respiratory bacterial infections
    • I. Pharyngitis- streptococcus pyogenes, corynebacterium diptheria
    • II. Epiglottitis- Haemophilus influenza type B (HIB)
    • III. Pertusis- bordetella pertussis
    • IV. Pneumonia- streptococcus pneumonia
    • a. Community-acquired (CAP)- more common
    • b. Hospital-acquired (nosocomial)
  19. All of the following statements concerning RSV are true except:
    • a. The virus contains a negative RNA genome
    • b. Large multi-nucleated cells may be seen in a nasal swab
    • c. A nucleotide analogue, Ribivirin, is used to treat infection in severely ill hospitalized patients
    • d. The virus is the leading cause for pneumonia in adults
  20. Which of the following viruses does not contain an envelope?
    • a. The virus that is the major cause for acute respiratory diseases in military recruits
    • b. The virus that is responsible for most of the viral pneumonia in infants
    • c. The virus that transcribes and replicates in the nucleus
    • d. The virus that caused severe respiratory syndrome in 2003-4, but is no longer detected in humans now
  21. Between 1919 and 1956, human Influenza was caused by viruses of H2N2 subtype, and there was a new pandemic. Which of the following processes was most likely responsible for the appearance of H2N2 virus?
    • a. Point mutations from error-prone viral RNA polymerase to generate a new subtype
    • b. Acquisition of the RNA segment that encodes a new subtype of NRA polymerase
    • c. Reactivation of latent H2N2 viruses in human carriers
    • d. Gene reassortment between human and animal influenza viruses
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virus WU.txt
virus WU Lung
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