Respiratory Viral Infections Flashcards
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
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
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
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
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
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
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
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
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
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
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)
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
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
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
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
