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UPPER RESPIRATORY TRACT
- 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
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LOWER RESPIRATORY TRACT
- 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
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COMMON COLDS
- 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
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RHINOVIRUSES
- 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
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CORONAVIRUSES
- 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
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ADENOVIRUSES
- 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
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PARAMYXOVIRUSES
- 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
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PARINFLUENZA VIRUSES (1-4)
- 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
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RESPIRATORY SYNCYTIAL VIRUS (RSV)
- 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
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INFLUENZA VIRUS
- 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
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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
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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
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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
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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
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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
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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
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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
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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)
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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
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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
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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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