Exam #4: Viral Infections of the Resp. Tract II Flashcards
List the characteristics of the Influenza virus.
- Orthomyxovirus
- -ssRNA
- Segmented,
- Enveloped (the envelope contains H & N)
- Hemagluttinin= viral attachment protein
- Neurominidase= cleaves sialic acid to aid in virion spread
What is the function of Hemagglutinin (H)?
- Attachment to host
- Agglutinates RBCs
What is the function of Neuraminidase (N)?
- Cleaves sialic acid
- Virion release
- Virion spread
What is antigenic drift?
- Small changes in virus e.g. H & N in Influenza
- Driven by point mutations made by RNA polymerase
- Significant changes occur every 2-3 years
*Why there are changes to the Influenza vaccine each year
What is antigenic shift & how is it different from antigenic drift?
- Large changes in H & N
- Driven by re-assortment of two viruses
- Requires co-infection of the same cell (less common than antigenic drift)
*The cause of pandemics
Describe the mechanism of re-assortment.
- Two different strains of a virus infect the same cell
- Replication occurs
- Assembly of virions is a “re-assortment” of viral particles
What kind of re-assortment is the most concerning in influenza?
Animal & Human strains re-assorting
E.g. Avian flu & Human flu reassortment
What are the barriers to re-assortment of human & animal species of Influenza?
Specializations for infection of humans vs. animals make it difficult for infection to occur simultaneously
I.e. human flu is good at infecting humans, avian flu is good at infecting birds, they’re both not very good at infecting the opposite. Since reassortment requires that a cell be infected with BOTH at the same time, this is a significant barrier.
What are the three different types of Influenza virus?
A, B & C
What are the characteristics of Influenza virus A? Specifically address # of genome segments, host range, disease severity, epidemic potential, and antigenic change.
- 8 segments
- Host= Humans, swine, avian, equines, marine mammals
- Disease often severe
- Causes Epidemics & Pandemics
- Undergoes antigenic drift & shift.
What are the characteristics of Influenza virus B? Specifically address # of genome segments, host range, disease severity, epidemic potential, and antigenic change.
- 8 segments
- Host= Humans ONLY
- Disease is occasionally severe
- Can cause outbreaks and occasional epidemics
- Undergoes antigenic drift ONLY
What are the characteristics of Influenza virus C? Specifically address # of genome segments, host range, disease severity, epidemic potential, and antigenic change.
- 7 segments
- Host= humans & swine
- Disease is usually mild
- Causes limited outbreaks
- Undergoes antigenic drift ONLY
So mild that vaccines are not even generated against Type C.
Which is the only type of influenza virus to be associated with antigenic shift?
Influenza A (most severe)
How are influenza viruses named clinically?
Serotype Location Isolate Year Hemagglutinin Subtype Neuraminidase Subtype
Which parts of the influenza virus are associated with antigenic shift?
H & N subtypes
What parts of the influenza virus are associated with antigenic drift?
Location
Isolate
Year
Outline the algorithm for antiviral treatment in influenza.
1) Mild or uncomplicated illness?
2) Does the patient have any Risk Factors?
Risk Factors= Treat with antiviral
No Risk Factors= If within 48 hours of the onset of symptoms, may consider antiviral
For both, provide instructions for symptomatic care, infection control, and return if no improvement in 72 hours
What are the classes of antivirals for influenza infection?
- Ion channel blockers
- Neuraminidase Inhibitors
What is the mechanism of action of Ion channel blockers?
Blocks replication prior to genome release by blocking the M2 ion channel
*Note that these are only effective against Influenza A & that most circulating Influenza A strains are resistant. CDC does NOT recommend their use.
What are the limitations of the Ion Channel Blockers?
- Effective only against influenza A
- Most Influenza A are not resistant
What drugs are Ion Channel Blockers?
Amantadine & Rimantadine
Mechanism of action of Neuraminidase blockers.
- Inhibit virion release & spread
- Active against influenza A & B
Names of Neuramindase
Zanamivir= oral inhalation
Oseltamivir (Tramiflu)= oral administraiton
Peramivir= IV
What are the limitations of Neuramindase inhibitors?
Must be given early to reduce disease symptoms/ duration.
What is IIV? How is it administered, what patients are eligible, and what is the strain composition?
Formaldehyde-inactivated influenza virus (IIV)
- IM or ID (intra-dermal)
- Widest age range & those with chronic medical conditions
- Trivalent or quadrivalent
What is LAIV? How is it administered, what patients are eligible, and what is the strain composition?
Live Attenuated influenza virus (LAIV)
- Intranasal
- Healthy, non-pregnant persons between 2-49 years old
- Quadrivalent
What does attenuated mean?
Less virulent form (cold resistant)
What is RIV? How is it administered, what patients are eligible, and what is the strain composition?
Recombinant Influenza Vaccine (RIV)- purified hemagglutinin protein
- IM
- 18-49 years
- Trivalent
What is the difference between the classic & novel method for influenza vaccine production?
Classic= production in embryonated chicken eggs
- Time intensive
Novel= production in mammalian cells (Madin Darby Canine Kidney)
- Faster
- Reduced likelihood of eff protein carryover
How is the recombinant influenza vaccine produced?
Baculovirus Expression Vector System (BEVS)
1) Insect virus made to express hemagglutinin protein
2) Large vats of cells grown & infected with virus
3) Cells produce Hemagglutinin
4) Hemagglutinin purified & used as vaccine
*Rapid scale up & “egg free” system
What do Trivalent vaccines contain?
2x A + 1x B
What do Quadrivalent vaccines contain?
2x A & 2x B
What is chemoprophylaxis & how is it implemented in regards to the flu?
- Daily dose of anti-viral for duration of flu season in the community
- Given to those at high risk for complications that are vaccinated after the flu seas has begun
- Given to health care workers & family members who care for those at high risk
What are the symptoms of SARS?
- Fever, malise, myalgia
- Dry cough & dyspnea
- ARDS
List the characteristics of the SARS Coronavirus.
- Coronavirus
- Enveloped
- +ssRNA
*More resistant to environmental conditions than non-SARS. Replicates well in warmer temperatures of the lower respiratory tract.
How is SARS transmitted?
- Fecal-oral
- Close contact
- Aerosol
How was the SARS virus controlled?
- Isolation
- Infection control measures
Authorities were able to identify individuals with fever via thermal-imaging & then isolate them. Fever precipitated sneezing & coughing, which were the main modes of transmission.
What is bronchiolitis?
Inflammation of the bronchioles (commonly seen in pediatric population)
Symptoms of bronchiolities.
- Exp. wheeze
- Nasal flaring
- Air Trapping
- Subcostal retractions
- Variable fever
What virus causes bronchiolitis?
Respiratory Syncytial Virus (RSV)
List the characteristics of RSV.
- Paramyxovirus family
- Enveloped
- -ssRNA
- Highly infectious
*The most common cause of bronchiolitis and pneumonia in children less than 1 year-old; however, severe disease can also be seen in the elderly & immunocompromised
How is RSV transmitted?
- Inhalation of large droplets
- Direct contact with respiratory secretion
How is RSV treated?
Aerosolized Ribavirin (antiviral)
What is the Ribavirin mechanism of action?
- Guanosine analog
- Inhibits nucleotide biosynthesis & mRNA capping
- Promotes hypermutation of the genome
When is Ribavirin indicated?
Indicated for severe lower respiratory tract RSV infection in special populations:
- Premature infants
- Patients with chronic lung disease
- Patients with congenital heart disease
- Immunocompromised patients
How is RSV prevented?
Passive RSV immunoprophylaxis= anti-RSV antibodies
When is RSV prophylaxis indicated?
- Birth less than 33 weeks gestation
- Greater than or equal to 2 years & have had therapy for chronic lung disease within 5 months prior to RSV season
What are the two RSV immunoprophylaxis agents?
1) Palivizumab= chimeric human-mouse monocloncal anti-RSV antibody
2) RSIG= pooled human Ig, enriched for anti-RSV antibodies
Note that there is a difference between RSV treatment & prevention, these only prevent, Ribavirin treats
What are the other viruses that can cause respiratory illness that have not been covered?
- Avian Influenza
- Cytomegalovirus
- Measles
- Varicella-Zoster
