L26-27: Viral Respiratory Tract Infections Flashcards
Where do more viral respiratory tract infections occur and why?
Upper respiratory tract due to cooler temperature – viruses tend to replicate better at 33-35 degrees C
Why can viral damage predispose patients to bacterial super-infections?
Mucociliary escalator is interrupted and immune system is weakened
Symptoms of the common cold
Rhinitis (inflammation of nasal mucosa) and pharyngitis (sort throat) but no high fever, LRT involvement, or respiratory distress
Incidence of the common cold
2-3 times per year in adults and 6-8 times per year in children; peak in spring and fall
Complications of the common cold
Otitis media, sinus infections, exacerbation of asthma (especially rhinovirus C)
Viruses associated with common cold
Rhinovirus, coronavirus, adenovirus, coxsackievirus
Characteristics of rhinoviruses
Picornavirus family member, non-enveloped, +ssRNA genome; three types are A, B and C and hundreds of serotypes
How are rhinoviruses transmitted?
Through direct contact with nasal secretions, large droplets, and contaminated fomites; extremely low inoculum needed for infection
How do rhinoviruses cause disease?
- -Virus infects nasal epithelial cells by entering and replicating
- -Virus causes damage inside the epithelial layer of tissue, leading to clear fluid outpouring
- -More and more cell damage as virus spreads
Why don’t we have vaccines for rhinoviruses?
There are more than 100 serotypes (but immune response can be long-lasting to particular serotype)
Characteristics of coronaviruses
Enveloped, +ssRNA genome, named for their sun-shaped appearance (non-SARS cause the common cold)
How is temperature preference different for non-SARS and SARS coronaviruses?
SARS viruses replicate better at body temperature, which is why they cause severe lower respiratory tract infection, while non-SARS viruses replicate at cooler temperatures
How does transmission of the non-SARS coronaviruses occur?
Through large droplets
Characteristics of adenoviruses
Adenovirus family, non-enveloped, dsDNA genome, fibers protruding from them are toxic to cells; no seasonal pattern of disease
Most common respiratory disease-causing serotypes for adenovirus
1, 2 and 5
What other illnesses can be caused by adenoviruses?
Pharyngoconjunctival fever (conjunctivitis, pharyngitis, and fever); more severe things such as croup, bronchiolitis, pneumonia; gastrointestinal disease
Characteristics of coxsackieviruses
Enterovirus subfamily of picornaviruses, non-eneloped, +ssRNA, fast replication, able to survive low pH conditions of GI tract
How are coxsackieviruses transmitted?
Fecal-oral route (occur more at daycare centers)
What else can coxsackieviruses cause?
Herpangina, hand-foot-&mouth disease
Hand-foot-&-mouth disease
Caused by coxsackievirus, symptoms include fever, vesicular lesions on hands and feet and oral areas; most frequent in children
Herpangina
Caused by coxsackievirus, symptoms include abrupt onset of fever, small vesicles on soft palate; most frequent in children 1-7 years
What other viruses can cause the common cold?
Influenza viruses (B and C), respiratory syncytial virus, and parainfluenza virus
What is croup?
Acute laryngotracheobronchitis, symptoms due to swelling in subglottic region of larynx
Symptoms of croup
Fever, distinct brassy cough comparable to seal’s bark, inspiratory stridor, narrowing of air shadow of trachea in radiograph (“steeple sign”), common cold-like symptoms
Why is croup more worrisome in younger children?
The younger the child, the smaller the airway, and less obstruction can occur before it conflicts with oxygen transfer
How do treatments differ based on whether a child has stridor at rest?
No stridor at rest –> humidified air, hydration
Stridor at rest –> oxygen, epinephrine, glucocorticoids
Types of parainfluenza virus
Type 1 is most common cause of acute croup, type 2-3 can also cause croup
Characteristics of parainfluenza virus
Paramyxovirus family, helical nucleocapsid, envelope with hemagglutinin and neuraminidase, -ssRNA genome
Transmission of parainfluenza virus
Large droplets and direct contact
Incubation period of parainfluenza virus
2-10 days
Symptoms of influenza
Myalgia, headache, fever, shaking chills, cough peaking between 3-5 days of illness, fatigue
Pneumonia
Inflammation of the lung parenchyma leading to abnormal gas exchange; symptoms include fever, chills, cough, pleural chest pain, increased respiratory rate, wheezes/crackles, hypoxia and cyanosis
2 types of pneumonia associated with Influenza virus
Primary Influenza virus pneumonia (usually Influenza A) and bacterial Influenza-associated pneumonia
Primary Influenza virus pneumonia
Caused by Influenza A usually, occurs more in children and ages 40+, symptoms begin mild and 1-4 days later more severe symptoms occur such as increased cough, tachypnea, dyspnea, acute respiratory distress
Sputum Gram stain for primary Influenza virus pneumonia
Abundant PMN cells without significant number of bacteria
Who is at risk for complication due to Influenza?
Children, 65+, pregnant women and women up to 2 weeks postpartum (also certain medical conditions)
Bacterial Influenza-associated pneumonia
Usually occurs one week after Influenza symptoms begin – flu symptoms lessen then increased cough, return of fever, and respiratory distress; Gram stain may contain bacterial cause
What are the main bacterial causes of bacterial Influenza-associated pneumonia?
S. pneumoniae, S. aureus and H. influenzae (also N. meningitidis, other streps, and Gram- Bacillus)
Characteristics of Influenza virus
Orthomyxovirus, segmented -ssRNA viral genome, enveloped, two important proteins are hemagglutinin (H) and neuraminidase (N)
Hemagglutinin (H)
Responsible for attachment, agglutinates RBC, important target for immune response
Neuraminidase (N)
Cleaves sialic acid, responsible for virion release and spread, important target for immune response
Antigenic drift
Small changes in H and N driven by point mutations made by polymerase during replication, causes significant epidemiological changes every 2-3 years (becomes completely different from original parent virus and this is the reason for changes in vaccines)
Antigenic shift
Large changes in H and N driven by reassortment of two viruses, occurs only with co-infection of the same cell, risk for pandemics (virus may end up so different immune system can’t identify it)
Where does reassortment occur?
Ex. Birds and humans have a hard time infecting each other, but when they interact with pigs the viruses can go back and forth between species (pig is like mixing vessel)
Differences between flu viruses A, B, and C: genome segments
A and B = 8 segments
C = 7
Differences between flu viruses A, B, and C: host range
A = humans, swine, avian, equines, marine mammals B = humans only C = humans and swine
Differences between flu viruses A, B, and C: disease severity
A = often severe B = occasionally severe C = usually mind
Differences between flu viruses A, B, and C: epidemic potential
A = often causes epidemics, pandemics B = causes outbreaks and occasional epidemics C = limited outbreaks
Differences between flu viruses A, B, and C: antigenic change
All types capable of antigenic drift, only A capable of antigenic shift
Antiviral treatments for Influenza
- Ion channel blockers
2. Neuraminidase inhibitors
Ion channel blockers
Includes Amantadine and Rimantadine, blocks replication prior to genome release (M2 channel blockers), only effective against Influenza A and currently viruses are resistant to these drugs
3 types of neuraminidase inhibitors
- Zanamivir (oral inhalation)
- Oseltamivir (oral)
- Peramivir (intravenous)
Neuraminidase inhibitor
Inhibit virion release and spread, active against A and B – causes clumping of virus on the surface of cells
Inactivated Influenza vaccines (IIV)
Formaldehyge-inacticated viruses, intramuscular (typical) or intradermal to patients at high risk/chronic medical conditions
Live attenuated Influenza vaccine (LAIV)
Attenuated viruses, intranasal, can be given to healthy, non-pregnant persons
Recombinant Influenza vaccine (RIV)
Hemagglutinin protein, intramuscular, can be given from 18-49 y/o
Vaccine production methods
Classic method = production in embryonated chicken eggs
Novel method = production in mammalian cells (MDCK cells)
Recombinant vaccine = egg-free system that is best for immunocompromised patients or those with egg allergies
Trivalent vaccines
2 Influenza A + 1 Influenza B strains
Quadrivalent vaccines
2 Influenza A + 2 Influenza B strains
Chemoprophylaxis for Influenza virus
Daily dose of anti-viral for duration of flu season in the community, given to those at high risk or when poor match between vaccine and circulating strains
Characteristics of SARS coronavirus
Coronavirus family, enveloped, +ssRNA genome, more resistant to environmental factors
Progression of SARS
Fever, malaise, and myalgia with dry cough and shortness of breath, most severe cases can cause adult respiratory distress syndrome (ARDS) and death
Transmission
Fecal-oral, close contact, and aerosol routes
Middle East Respiratory Syndrome (MERS)
Similar to SARS, spreading around Middle East
Bronchiolitis
Inflammation of the bronchioles, symptoms include expiratory wheezing, nasal flaring, air trapping, subcostal retractions, and variable fever – often severe in infants due to small size of tissues
Respiratory Syncytial Virus (RSV)
Most common cause of bronchiolitis and pneumonia in children <1 y/o, paramyxovirus family, enveloped, -ssRNA genome, highly infectious
Transmission of RSV
Inhalation of large droplets or direct contact with respiratory secretion
Ribavirin treatment for RSV
Aerosolized, guanosine analogue that inhibits nucleotide biosynthesis/mRNA capping and promotes hypermutation of the genome – only indicated for severe LRT RSV infections
Prevention of RSV
Passive immunoprophylaxis for preemies and <2 y/o with chronic lung disease
Agents for RSV passive immunoprophylaxis
Palivizumab (chimeric human-mouse monoclonal anti-RSV antiboy) and RSIG (pooled human immunoglobin)
Other viruses that cause respiratory illness
Avian Influenza, Cytomegalovirus, measles and Varicella-Zoster (with pneumonia as a complication)
