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Flashcards in Respiratory Viral Infections Deck (17):
1

Identify the peak seasonal disease incidence (midwinter; Spring/Fall; no particular seasonality) due to the RSV, influenza viruses, rhinoviruses, parainfluenza viruses, coronaviruses, and adenoviruses

• Respiratory syncytial virus = winter peak
• Influenza viruses = winter
• Rhninoviruses = 2 peaks (Sept.-Nov. & April-June)
• Parainfluenza viruses = 2 peaks (Oct.-Nov. & May-June)
• Coronaviruses = winter
• Adenoviruses = no seasonality
• Enteroviruses = late summer/early fall

2

RSV treatment options

For hospitalized infants:
• Aerosolized ribavirin (but debate about efficacy)

For prevention in high-risk patients
• Palivizumab = monoclonal Ab against RSV fusion protein
• Also used to treat severe cases

Breast feeding also helps protect infants
• Anti-RSV Ab’s secreted by mother

3

Describe and explain the lower respiratory manifestation (bronchiolitis) caused by
RSV and discuss how it is diagnosed and treated.

LRT infections:
o Bronchitis
o Croup
o Bronchopneumonia
o Pneumonia

Epidemiology:
o Major cause of respiratory illness in children 6 months to 1 year
o Boys hospitalized > girls
o Problem in adults >65 years with COPD

Clinical signs:
o Incubation 2-8 days
o Nasal congestion, sore throat, fever (lower than flu), cough; followed by dyspnea and wheezing
o X-ray: interstitial infiltrates and hyperinflation
o Rare: bronchiolitis, pneumonitis, bronchitis, croup
o Common complications: otitis media, sinusitis

Prevention
o Vaccines currently in trial

Therapy
Antivirals within 48 hours of onset
• Ribivarin approved for hospitalized infants (but questionable efficacy)
• RSV immune globulin = premature infants in first year
• Palivizumab = monoclonal Ab against F protein used in high risk children
Supportive
Oxygen and ventilator support

4

Influenza virus: clinical manifestations

Uncomplicated “Flu”
o Abrupt onset (1-2 days incubation)
o Symptoms: fever, myalgia, malaise, dry cough, sore throat, nasal congestion
• NOT common: GI symptoms, rhinorrhea
o Systemic symptoms: last 3-5 days
• Due to systemic cytokines from infected respiratory tract
o Respiratory symptoms: last another 3-4 days more
o Recovery of lung function may take weeks

Can cause more serious complications:
1) Pneumonia
• Begins like classic flu
• Progresses to dyspnea and cyanosis with mixed hypoxia
• X-ray findings: no lobar consolidation; see interstitial pattern
• At risk: young children, elderly, patients with lung disease (COPD, asthma), heart disease, pregnant women
2) Secondary bacterial pneumonia
• Classic influenza with improvement
• Then = fever, cough, sputum production, lung consolidation (x-ray)
• 3 common bacterial causes: S. pneumonia, S. aureus, H. influenzae
• More common in elderly and patients with lung disease
3) Other rare complications: myositis, myocarditis, Guillain-Barre syndrome, Reye’s syndrome

5

Influenza virus: Prevention

Hygiene = wash hands

Vaccines:
Standard vaccine
• Killed virus
• Short-lived protection
• Repeat yearly
Flumist
• Live attenuated virus
• Repeat yearly
• Not for children less than 5 yrs, adults over 50 years; other restrictions

6

Influenza virus: treatment

Antivirals

Amantidine/Rimantidine
• Bin to M2 ion channel protein → blocks uncoating
• But many viruses now resistant

Tamiflu/Relenza (oseltamivir, zanamivir)
• Inhibit neuraminidase → blocks release of virus from cells
• Must be started within 48 hours of onset

7

Influenza virus: Reassortment

o Only occurs with viruses with segmented genomes (ex: influenza!)
o Infection of same cell with 2 different strains → random packaging of genome segments
o 1 or more genes can be transferred between strains
o Can lead to different properties

Ex: with influenza virus
• Causes periodic pandemics
• Due to reassortment event = replaces gene segments
• Hemagglutinin: envelope glycoprotein involved in attachment and entry
• Neuraminidase: envelope glycoprotein involved in efficient viral release from cells
• Results in new HA → never seen in population → not protected

8

Antigenic shift vs antigenic drift

Antigenic Shift = reassortment event that introduces a new gene segment into circulating human influenza virus strain

Antigenic drift = point mutations in currently circulating human influenza strain that alters virulence slightly or reduces

9

Process of generating re-assorted influenza:

o Human strains have only 3 HA proteins
o Others = from birds
• Pandemic reassortment from new bird HA jumping into human background strain

Requires a Mixing vessel: species permissive for replication of both human and avian flu viruses
This case = pigs
• Can be infected with both (depends on receptor specificity)
• Avian strains = α2,3-linked sialic acid
• Human strains = α2,6-linked sialic acid
• Pigs = have both

Most pandemic strains have come from Southeast Asia
• Due to farming practices
• Feed pigs duck feces = transmits virus to pigs
• Avian influenza = enteric infection, so high titers shed in feces

As of now = not transfer directly from birds to people, or is transmitted person-to-person

Result of temporary immunity and antigenic shift = vaccines only protective for 1 year

10

Parainfluenza virus

2nd to RSV as a LRT infection in children

4 serotypes
• Clinical presentation differs between types
• Types 1 & 2 = more severe disease in boys
• Type 3 = no gender differences

Incubation 2-7 days

Starts as “cold” sometimes with bronchitis; may have low grade fever for 2-3 days
• Types 1 & 3 = can progress to croup (severe lung irritation and distinctive wheezing cough)
• Type 3 = can progress to pneumonia or bronchiolitis
• Type 4 = rarely causes severe disease

Re-infections are common

Prevention:
• No antivirals
• No vaccine
• Good hygiene and hand washing

Therapy:
• Supportive
• Hospitalization for severe cases (croup)
• Oxygen and possible ventilator support

11

Adenoviruses

o Most people infected with at least 1 serotype by age 10
o Appears to be latent in adenoids and tonsils

Infections = primarily sporadic, can cause outbreaks in institutions
• Can be spread in stools and via wet secretions

Clinical presentation:
• Infants: cough, sore throat
• Children: sore throat, tracheitis
• Young adults: more severe with cough, fever, sore throat, runny nose
• Adults: “cold”
• Immunosuppressed = can progress to pneumonia with dissemination, cystitis, and CNS infection

Therapy
• No antivirals
• Symptomatic treatment

Vaccine
• Encapsulated respiratory types swallowed
• Causes asymptomatic infection in gut
• Wild type strains (not attenuated or killed)

12

Coronaviruses

o Cause 15% of all colds
o Periodic epidemics; peaks in winter and spring
o Common re-infection

Clinical presentation:
• “Common cold”
• Headache, sore throat, cough, malaise, sometimes low grade fever
• Less common = runny nose
• Can cause gastroenteritis → diarrhea
• Can exacerbate asthma and COPD symptoms

SARS CoV:
• Starts with 2-7 days of mild URT symptoms
• Progresses to fever, rigors, dry cough, dyspnea, malaise, headache, influenza-like illness
• 27% also have diarrhea

Results: severe inflammatory response with fluid build-up in lungs (Acute Respiratory Distress Syndrome)
• Diffuse alveolar damage
• Desquamation
• Hyaline membranes
• Alveolar edema
• Inflammation
• Syncytia formation
• Thickened alveolar walls
• 2002 outbreak thought to be contained

13

Identify the major groups of "common cold" viruses

Influenza A, B, C
Enterovirus (71 types)
Adenovirus (42 types)
Parainfluenza Types 1-4
Respiratory Syncytial virus
Rhinovirus
Coronavirus
Metapneumovirus
Human Bocavirus
WU virus

14

Describe how the common could viruses are transmitted from person to person

o Viruses replicate in respiratory epithelial cells → cell death, sloughing, paralyzed ciliary action
o Debris clogs airways

Cytokine release:
• Muscle aches, fever, malaise
• Airway inflammation
• Edema and fluid build-up
• ARDS:
• First seen in SARS but occurs with others
• Massive inflammation and fluid-build up in lungs

15

Rhinoviruses: Epidemiology

Cause 30-40% of all colds
o Compare to Coronaviruses (~10%) and enteroviruses (<10%)
o Smoking = not predispose but causes more severe symptoms

16

Rhinoviruses: Clinical presentation

Sneezing, runny nose, sore throat, cough, nasal congestion (may be severe), headache, little or no fever
• Usually NO myalgia and fatigue

Can exacerbate asthma and bronchitis:
• Triggers eosinophil infiltration into lungs

Common complication = otitis media, sinusitis

17

Rhinoviruses: Treatment

o Treat symptoms = OTC antihistamines, decongestants
o No antivirals
o Vitamin C = little evidence for efficacy
o Zinc = some evidence for efficacy
o Echinacea = boosts immune response, efficacy not shown in trials