Viral Respiratory Infections:

Front 1

This lecture goes over the pathophysiology of viral infections in which locations?

Back 1

-nose and throat
-larynx and trachea
-large bronchi
-bronchioles

Front 2

What are the four major viral respiratory pathogens discussed in this lecture?

Back 2

1.) rhinovirus
2.) parainfluenza virus
3.) influenza virus
4.) respiratory syncytial virus

Front 3

Go over the epidemiology of respiratory tract infections: -adults infected / year vs. children infected per year
-amount of restricted activity days/ year
-percent of infections caused by viruses

Back 3

adults: 1-4 infections per year
children: 6-8 infections per year

influenza-like illnesses result in 400 million days of restricted activity/ year

65-75% caused by viruses (more than 200 viruses from 10 distinct genera)

Front 4

What is a major determinant of clinical manifestations?

Back 4

anatomical location

Front 5

There are overall twelve different clinical manifestations linked to specific areas in the body. can you list them?

Back 5

Front 6

Depending on causative agent, different clinical manifestations of respiratory infection can occur. list problems caused by viruses, bacteria, and fungi:

Back 6

viruses: upper respiratory tract
bacteria: (OSEP): otitis media, sinusitis, epiglottitis, pneumonia
fungi and protozoa: important cause of pneumonia in the immunocompromised

Front 7

There are 5 anatomic locations of infection and each is associated with common pathogens. Give the list of infection location to pathogen:

Back 7

Nasopharynx: rhinovirus, coronavirus, other respiratory viruses
Oropharynx: Group A streptococcus, EBV, adenovirus, HSV, enterovirus
Middle Ear and sinuses: Strep pneumonia, H. influenzae, moraxella catarrhalis
Bronchi: strep pneumonia, H. influenza, mycoplasma pneumoniae and influenza
Bronchioles: RSV

Front 8

Give a list of the most common illnesses associated with respiratory viruses:

Back 8

Front 9

Infections of the nose and the throat: five aspects of pharyngitis:

Back 9

1.) infection of the oropharynx
2.) discomfort in throat, especially during swallowing
3.) nasal symptoms may also be present
4.) viruses more common than bacteria
5.) viral pharyngitis can NOT be distinguished from bacterial pharyngitis on clinical grounds (culture for Group A Streptococcus);

Front 10

Infections of the nasopharynx: 3 important aspects:

Back 10

1.) most are viral
2.) lead to signs and symptoms associated with the common cold
3.) primary etiology is the rhinovirus

Front 11

Draw a table listing the etiological pathogens associated with the common cold: 9 pathogens total/ with established % of cases and peak season

Back 11

pathogens:
rhinovirus: (30-50%); all seasons
coronavirus (10-15%); winter
influenza (5-15%); winter
the 5 5% ers'!
RSV (5%; winter)
parainfluenza: autumn/ spring
enterovirus: summer
adenovirus: all seasons
HMPV: winter

Front 12

What are important points concerning the epidemiology of the common cold?

Back 12

-very common infections (adults = 1 infection/ year; children and parents: 3-5 infections / year)
-occurs during the fall and the spring
-multiple serotypes of rhinovirus circulate (102 serotypes exist)

infected humans are the only reservoir

TRANSMISSION: contamination of hands and direct contact with mucus membranes; cold temperatures and fatigue = not associated

Front 13

Give a sample flowchart for the transmission of a rhinovirus:

Back 13

1.) nasal secretions of infected person --> hand of infection person --> direct or fomite such as telephone --> hand of susceptible person --> nose or eyes of susceptible person --> viral replication in nasal mucosa

Front 14

Describe four important points in the pathogenesis of the common cold:

Back 14

1.) small innoculum is sufficient to initiate an infection
2.) virus binds to specific receptors on respiratory cells:
a.) 91 serotypes use ICAM-1
b.) 10 serotypes use LDL-R
c.) 1 serotype uses Decay-accelerating factor
NOTE: there is spread to the respiratory epithelium by local extension AND the posterior pharynx is the site of the most intense infection
viremia/ infection of sites OUTSIDE the respiratory tract does not occur

Front 15

WHAT IS THE MECHANISM of symptom production in the common cold? (leads to sneezing/sore throat; rhinorrhea; cough, nasal obstruction)

Back 15

viral infection of nasal cells:
a.) chemical mediators of inflammation:
b.) sensitization and irritation of airway receptors:

Front 16

How do you prevent the common cold?

Back 16

a.) immunity against only the serotype affecting
-antibody blocks attachment to cellular receptor
b.) vaccine is not feasible:
-serologic diversity in rhinoviruses
-rhinoviruses account for only 50% of colds

Front 17

How do you treat the common cold once you have it?

Back 17

NOTHING really: no approved antivirals; medications for symptomatic treatment do not alter course of illness
-other therapies (zinc, echinacea, vitamin C = no benefit)

Front 18

INFECTIONS OF THE LARYNX AND THE TRACHEA: CROUP list five important characteristics of croup:

Back 18

1.) obstruction of upper airway with sudden onset of a barking cough, difficulty breathing, and stridor
2.) almost all cases = PARAINFLUENZA VIRUSES ---> croup = parainfluenza
3.) usually preceded by 1-3 days of nasal discharge and dry cough
4.) self-limited: resolves in 3-7 days
5.) In adults: manifestation is usually hoarseness

Front 19

Differentiate between croup and epiglottitis:

Back 19

croup: viral, effects airway below the vocal cords; inspiratory stridor

epiglottitis: bacterial (primarily Hib); effects the epiglottitis; and muffled voice with drooling

Front 20

three important points for the pathogenesis of croup:

Back 20

1.) virus spreads by direct extension
2.) no viremia or infection OUTSIDE the respiratory tract
3.) histamine and IgE antibodies to parainfluenza virus are found in nasopharyngeal secretions (therefore, immunologic mechanisms involving inflammatory mediators may be involved in pathogenesis)

Front 21

pathogenesis of upper airway obstruction in croup: 4 different points:

Back 21

1.) edema of the tracheal mucus membrane
2.) tracheal wall has nonexpandable rings of cartilage
3.) mucus membrane swelling results in narrowing of tracheal lumen
4.) worsens during inspiration resulting in inspiratory stridor

Front 22

Therapy of croup:

Back 22

1.) supportive care
2.) to reduce edema and relieve airway obstruction use oral corticosteroids and inhaled epinephrine

Front 23

INFECTION OF THE LARGE BRONCHI: etiology of bronchial infections: What is the most common agent and three other agents:

Back 23

influenza is the most common viral agent
may be also caused by mycoplasma, other viruses, and bacteria (i.e. in patients with COPD)

Front 24

INFLUENZA: general features and demographics of influenza:
affects on adults vs. young and elderly
-amount of money spent in the US:

Back 24

-a major epidemic disease in developed countries
-a relatively mild disease in normal adults but significant mortality in elderly and immunocompromised

-toll of influenza in the US:
-25 million physician visits
-125,000 hospitalizations, 25,000 deaths ; 2.5 billion in medical costs

Front 25

Influenza virus features: the three types and what is the outer coat made of?

Back 25

three serotypes A,B,C:
-neuraminidase and hemagglutinin proteins which determine virulence

Front 26

classification scheme: how are new strains named?

Back 26

TYPE/ CITY or country of first isolation/ Recovery year/ subtypes

Front 27

Antigenic drift: Describe some features of antigenic drift?

Back 27

-influenza types A and B
-modest variations (point mutations) in hemagglutinin and neuraminidase genes
-antigenic profile changes may compromsie vaccine and immune system efficacy
-annual evaluation of circulating influenza and vaccine reformulation updates antigenic profile
-responsible for annual epidemics

Front 28

Antigenic shift: describe some features of antigenic shift?

Back 28

-only influenza type A;
-profound variation in hemagglutinin or neuraminidase structure
-mixture of genes from diff. virus strains through genetic reassortment
-animals are likely reservoirs for genes for new strains

-new virus with novel antigenic profile
-compromised vaccine and immune system efficacy
-PANDEMIC consequences

Front 29

Transmission of influenza:

Back 29

inhalation of large and small aerosols caused by coughs or sneezes

Front 30

epidemiology of influenza (2 different slides); list some important features in the epidemiology

Back 30

-occur in US on an annual basis
-late fall to late winter
-most outbreaks are mild and sporadic
-every few years there are severe epidemics
-pandemics (frequent disease worldwide): occur rarely: 1918, 1957, 1968, 2009)

Front 31

Define endemic, epidemic, and pandemic

Back 31

endemic: (sporadic): most of the population is immune
epidemic: antigenic drift has led to a large number of nonimmunes
pandemic: antigenic shift leaves nearly all persons susceptible

Front 32

What parts of the respiratory tract does influenza infect and what happens when person has partial immunity to neuraminidase?

Back 32

-infects upper and lower respiratory tract cells
-partial immunity to neuraminidase may confine infection to upper respiratory tract

Front 33

What does the destruction of ciliated bacteria provide a foothold for?

Back 33

-for superinfecting bacteria;
-secondary bacterial pneumonia; usually lobar and pneumococci, staphylococci, and H. influenzae

Front 34

Draw a flowchart outlining the viral infection and lysis of respiratory epithelial cells:

Back 34

Front 35

Comparison of common cold versus the flu in 9 different subpoints:

Back 35

1.) fever: cold (rare in adults and common in children); flu (usually 1-2 but up to 104 and lasts 3-4 days)
2. headache: cold (rare) and flu (sudden onset and can be severe)
3.) muscle aches: cold (mild) and flu (usual and often severe)
4.) tiredness and weakness: cold (mild) and flu (last two or more weeks)
5.) extreme exhaustion: cold (never) and flu (sudden onset)
6,7,8: runny nose, sneezing, and sore throat features of common cold/ flu only sometimes
9.) COUGH: (common cold : mild hacking) and flu = usual and can become severe

Front 36

Diagnosis of influenza: 3 different ways:

Back 36

1.) on epidemiologic grounds
2.) on viral culture
3.) rapid viral assays (EIAs and PCR)

Front 37

treatment of influenza:

Back 37

supportive care
-antivirals: RAN: (zo)
rimantidine and amantidine: prophylaxis and treatment ; influenza A only

neuraminidase inhibitors:
zanamivir (inhaled) and oseltamivir (oral)
-treatment and prophylaxis: influenza A and B

Front 38

influenza vaccines approved in the US:

Back 38

vaccines contain three viral strains (usually 2 type A and 1 type B); composition changed annually to reflect current strains; this year = h1n1 and H3n2 and a b strain
1.) trivalent inactivated vaccine (intramuscular injection)
2.) live attenuated vaccine (intranasal administration)

Front 39

INFECTIONS OF THE BRONCHIOLES: bronchiolitis:

Back 39

-airway obstruction with wheezing and air trapping
-most commonly caused by respiratory syncytial virus

Front 40

6 different pathogens and associated relative importance of each: for bronchiolitis:

Back 40

RSV: +++
parainfluenza 3: ++
parainfluenza 1: +
parainfluenza 2: +
adenovirus +
influenza +

Front 41

epidemiology of RSV:

Back 41

seasonal disease: epidemics every winter
-almost all children are infected but only 1% need hospitalization
-humans = only reservoir
-risk groups: congenital heart disease, immunodeficiency, chronic pulmonary disorders

Front 42

What is this a picture of and why does it happen?

Back 42

-pathogenesis of RSV bronchiolitis
-necrosis of epithelial cells lining small bronchioles
-increased mucus secretion, inflammation, and edema

Front 43

What is this a picture of?

Back 43

-pulmonary infiltrates for RSV pneumonia
-alveolar involvement with swelling of alveolar lining cells and interstitial inflammation

Front 44

Other aspects of pathogenesis of RSV:

Back 44

-transmission occurs by direct contact with infected secretions
-spread occurs cell-cell down the respiratory tract
-no extra respiratory disease occurs
-self limited and can cause bronchiolitis and pneumonia

Front 45

Draw a flowchart for the pathogenesis of bronchiolitis:

Back 45

Front 46

Treatment of RSV infections:

Back 46

-

Front 47

Treatment of RSV infections:

Back 47

-usually a self-limited illness
-primarily supportive with oxygen and hydration
-bronchodilaters are sometimes useful
-steroids are NOT effective in randomized trials
antiviral: ribavirin by inhalation (rarely given)

Front 48

Prevention of RSV infection: what prophylaxis is used and what vaccine is under development?

Back 48

-prophylaxis with anti-RSV monoclonal antibody (palivizumab) in high risk infants
premature infants and infants < 2 with COPD and congenital heart disease

also live attenuated cold-adapted vaccine is under way