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MHD2 > Block 11 - L3-5 > Flashcards

Block 11 - L3-5 Flashcards

1
Q

What are two prominent viral causes of respiratory disease?

A
  1. Orthomyxoviruses (influenza)

2. Paramyxoviruses (respiratory syncytial virus and parainfluenza virus)

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2
Q

What is the most common route of viral infections (including influenza virus)?

A

Inhalation (aerosol droplets can contain viruses)

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3
Q

What is the incubation period for the influenza virus?

A

1-3 days

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4
Q

Influenza virus shedding precedes symptoms by how many days?

A

1 day

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5
Q

What are the symptoms of influenza?

A 
Central - headache
Systemic - fever (usually high)
Muscular - extreme tiredness
Joints - aches
Nasopharynx - runny or stuffy nose, sore throat, aches
Respiratory - coughing
Gastric - vomiting
CXR - lung consolidation
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6
Q

What causes the symptoms of influneza?

A

Cytopathic infection and immune response

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7
Q

How does the influenza virus cause ARDS?

A
  1. Infects epithelial cells of the respiratory tract
  2. Cell die (direct effects of the virus + interferon)
  3. Efficiency of ciliary clearance is reduced, impairing the mucus elevator
  4. Reduced clearance of infectious agents from the tract
  5. Gaps in the protective epithelium provide other pathogens access to other cells
  6. Bacterial pneumonia can develop; ARDS can develop
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8
Q

What is almost never observed in influenza virus infection?

A

Viremia

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9
Q

Which populations can experience severe cases of influenza?

A

Co-morbidities: asthma, COPD, CHF, obesity, bacterial pneumonia, immunosuppression and cytokine dysregulation

Patient populations: infants (smaller airway passages), pregnant or <2 weeks postpartum, age (<5 and >65)

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10
Q

Which type of influenza causes ~70% of human disease?

A

A (B and C cause the remaining 30%)

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11
Q

Describe the structure of influenza.

A

Enveloped negative-strand segmented RNA virus with a pleomorphic structure and 8 single-stranded negative-strand RNA strands in each particle

HA (hemagglutinin) and NA (neuraminidase) stud the particle

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12
Q

Which viruses can be killed by organic solvents and why?

A

Enveloped viruses such as influenza can be killed by organic solvents (dissolve the lipid envelope)

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13
Q

What is the infection cycle of the influenza virus?

A
  1. One virus enters cells apically and newly-made progeny viruses (1000+) egress after 10 hours (apically)
  2. Enter host cell nucleus and are transcribed; exit to cytoplasm and are translated to viral proteins (including polymerases which return to the nucleus to amplify infection)
  3. Move to the plasma membrane to form platforms for viral budding and epical egress
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14
Q

Where do anti-viral antibodies bind on the influenza virus?

A

Epitope sites on HA

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15
Q

How do influenza epidemics occur?

A

Antigenic drift caused by point mutations, particularly in the hemagglutinin spikes

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16
Q

How doe influenza pandemics occur?

A

RNA segment reassortment leading to antigenic shifts (8 RNA segments, influenza is widespread in different animals)

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17
Q

How are influenza virus vaccines made?

A

Strains are grown in chicken eggs, purified from allantoic fluids, inactivated, quality-controlled, and injected intramuscularly; live-attenuated vaccine is also available for intranasal delivery

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18
Q

How long does it take for protective antibodies to form after flu vaccination?

A

2-4 weeks

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19
Q

Antibodies against the influenza virus target what aspect of the virus?

A

Bind to HA proteins and prevent virus entry and membrane fusion

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20
Q

How are influenza virus vaccines classified?

A
  1. Serotype (A, B, C)
  2. Geographic location of the isolate
  3. Host of origin
  4. Strain number and year of isolation
  5. HA and NA subtypes
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21
Q

What are the four laboratory tests that can be used to diagnose influenza virus?

A
  1. Immunofluorescence (rapid and specific, but labor-intensive/requires quality reagents)
  2. Enzyme immunoassay (rapid and can be automated, but expensive and can be insensitive)
  3. Culture (confirms infective virus, but is slow and some viruses cannot be cultivated)
  4. PCR (fast, sensitive, and specific, and expensive with some false-positives)
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22
Q

What are the two types of anti-influenza drugs and what do they target?

A
  1. Amantadines (target M2)

2. NA inhibitors (target NA)

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23
Q

Describe the MOA of amantadines.

A

Prevent M2 (ion channel) from functioning; this prevents the interior of the flu virus particles from becoming acidified in the endosome during entry; normally, this acidification loosens up the contacts between RNA and M1 to allow the RNA to flow into the cytoplasm

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24
Q

Describe the MOA of neuraminidase inhibitors.

A

NA is a receptor destroying enzyme that strips away sialic acids from infected cells, so that when new viruses bud off of the infected cells, they will not re-bind back onto the same cell from which they arose; when NA is blocked, the viruses will re-bind, restricting the infections to a localized area. In other words, these drugs retard virus dissemination.

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25
What are some additional common respiratory viruses?
``` Rhinovirus Coronavirus Adenovirus Influenza Para-flu and RSV HSV and EBV ```
26
True or false - the same virus can cause different disease patterns (bronchiolitis, common cold, croup, influenza-like pneumonia) depending on the extent of infection and host response.
True
27
True or false - Rhinoviruses, Adenoviruses, and Coronaviruses can all cause the common cold.
True
28
Rhinoviruses cause acute infections in the ___. Vaccines are of limited utility - why?
Respiratory tract; diversity (hundreds) of serotypes
29
Adenoviruses cause infections in the respiratory tract, as well as ___ (aka ___). There is a live-attenuated vaccine to some serotypes, but no antiviral drugs yet.
Conjunctivitis; pink eye
30
Coronaviruses can cause both respiratory and ___ infections. They are common in children and often cause ___.
GI; croup
31
Small changes in the surface glycosylation of the influenza virus are called ___.
Camouflage (block antibody binding site)
32
What is the genome and family of influenza virus?
Segmented negative strand RNA orthomyxovirus
33
How is influenza virus most common transmitted?
Respiratory
34
What is the current method of detection of influenza virus?
Film array RT-PCR assay
35
What is the mechanism of pathogenesis of influenza virus infection
Exuberant immune responses cause lethargy, muscle aches, fever while necrotic infected cell debris and inflammatory infiltrates occupy airways and impede breathing
36
Are there any anti-viral therapies available against influenza virus?
Amantidine or Neuraminidase inhibitors (tami-flu)
37
Are there any vaccines available against influenza virus?
1. Live-attenuated vaccine (flu-mist) | 2. Killed virus vaccines with current year HA and NA
38
Why do people need to be vaccinated annually for influenza virus?
Because new influenza strains arise due to antigenic drift and antigenic shift
39
What causes pandemic influenza virus outbreaks?
RNA segment reassortment causing antigenic shift
40
What are common causes of respiratory infections?
Viruses (82%) - rhinovirus, parainfluenza virus, influenza virus, RSV, adenovirus, enterovirus Bacterial (13%) - GAS Mycoplasma and other (4%)
41
When do influenza and RSV present temporally?
Winter (peak)
42
What are the viruses in the paramyxoviridae family?
1. Parainfluenza (types 1-4) 2. Mumps 3. Measles 4. RSV (types A and B) 5. Metapneumovirus (types A and B)
43
How does RSV present in infants/young children, adults, and elderly?
Infants/young children - LRTI Adults - milder URTI Elderly - pneumonia
44
How is RSV transmitted?
Respiratory (generally requires close contact)
45
What type of patient is at high risk for complications of RSV?
Infants who are premature, immunocompromised, or have congenital heart disease
46
Discuss the pathology of RSV infection.
Necrosis of bronchiolar epithelium in 18-24 hours, submucosal edema, bronchioles occluded with mucus and cellular debris, hyperinflation and air trapping
47
How are respiratory specimens worked up?
RT-PCR (1-3 hours, FilmArray Respiratory Panel tests for 20 pathogens)
48
What is the preventive treatment for RSV in high-risk infants?
Palivizumab - humanized Ig - expensive but effective
49
What is the MOA of Palivizumab?
Monoclonal Ab that binds RSV F (fusion) protein, prevents attachment to the cell
50
What is human metapneumovirus (hMPV)?
A new virus that presents similarly to RSV, with a less severe disease outocme
51
Discuss the features of parainfluenza virus infections.
Large, relatively unstable enveloped virion, easily inactivated Contagion period precedes symptoms and may occur in the absence of symptoms Human hosts only Reinfection can occur later in life
52
How is parainfluenza virus transmitted?
Inhalation of large droplet aerosols
53
How does parainfluenza virus infection present in children and adults?
Children - mild disease, crou Adults - reinfection with midler symptoms Infection is limited to the respiratory tract, URT infection is most common, though LRT infection can occur
54
What is the geographic and seasonal preference of parainfluenza virus?
Ubiquitous, worldwide, seasonal
55
Discuss the various presentations of parainfluenza virus.
NOT systemic, no viremia Coldlike symptoms, bronchitis, bronchiolitis, croup (laryngotracheobronchitis)
56
What type of protective immunity develops after infection with parainfluenza?
Protective immunity of relatively short duration
57
What is another viral cause of croup?
Human coronavirus NL-63
58
Which type of parainfluenza virus is most common?
Type 3
59
What are the genomic features of paramyxoviridae viruses?
Negative single strand RNA viruses that induce cell fusion (syncytium formation)
60
How does RSV appear in tissue culture?
Syncytia - amalgamation of cells with the loss of cell border, multinucleated cells, intracytoplasmic inclusions
61
Of the 4 major types of paramyxoviruses (parainfluenza, mumps, measles, RSV), which have fusion proteins?
All
62
Of the 4 major types of paramyxoviruses (parainfluenza, mumps, measles, RSV), which have hemagglutinin?
Parainfluenza Mumps Measles (NOT RSV)
63
Of the 4 major types of paramyxoviruses (parainfluenza, mumps, measles, RSV), which have neuraminidase?
Parainfluenza Mumps (NOT measles or RSV)
64
Of the 4 major types of paramyxoviruses (parainfluenza, mumps, measles, RSV), what type of immunity develops for each?
Short-lived - parainfluenza, RSV Life-long - mumps, measles
65
Of the 4 major types of paramyxoviruses (parainfluenza, mumps, measles, RSV), which have multiple antigenic types?
Parainfluenza - 4 | RSV - 2
66
Of the 4 major types of paramyxoviruses (parainfluenza, mumps, measles, RSV), which have a vaccine?
Mumps and measles (both live-attenuated) RSV - in development
67
What is the most common disease associated with RSV?
Severe lower respiratory tract infection in children
68
How is RSV usually transmitted?
Inhalation of respiratory droplets
69
What is the current recommended mode of detection for RSV?
Film array RT-PCR of nasal wash
70
What is the pathogenesis of RSV?
Necrosis of bronchiolar epithelium in 18-24 hours, submucosal edema, bronchioles occluded with mucosa and cellular debris, and hyperinflation and air trapping
71
Are there any effective anti-viral agents available for treatment of hospitalized children with RSV?
No
72
Are there any effective therapeutics against RSV?
Administer Palivizumab prior to infection
73
Is there a vaccine currently available for RSV?
No
74
Are there any long-term consequences to RSV infections?
Less severe reinfection and short-term immunity
75
How is mumps transmitted?
Respiratory droplets
76
Discuss the pathogenesis of mumps virus.
Respiratory tract is inoculated, local replication occurs, infects epithelial cells of the respiratory tract, spreads systemically by viremia to: parotid gland, testes, CNS Less commonly - peripheral nerves, eye, inner ear, pancreas
77
What is the incubation period of mumps infection?
7-14 days
78
What is the classic symptom of mumps?
Swelling of parotid glands
79
What component of host defense is necessary to combat mumps?
CMI (Ab is not sufficient due to mumps' ability to spread cell to cell) Note - CMI is partly responsible for symptoms
80
What is the clinical definition of mumps?
Acute onset of unilateral or bilateral swelling of the parotid or salivary gland lasting >2 days without another apparent cause
81
What is the lab criteria for diagnosis of mumps?
Isolation of mumps virus OR Significant increase in mumps IgG Ab level between acute and convalescent samples OR Positive serologic test for mumps IgM Ab
82
Describe the features of the mumps vaccine.
Live-attenuated, 95% effective, lifelong immunity, 1 dose + 1 boost, administered with MMRV
83
What is a leading cause of vaccine-preventable deaths in children?
Measles
84
What are the symptoms of measles?
Characteristic maculopapular rash, coryza, cough, conjunctivitis, Koplik's spots (grain-of-salt appearance in mouth)
85
What are possible complications of measles?
Diarrhea, oitis media, croup, bronchopneumonia, encephalitis and subacute sclerosing panencephalitis
86
What is the incubation period of measles?
~7 days
87
What is the course of measles?
7 day incubation period ~1 week of viremia, viriuria, viral shedding Rash presents between day 10-14
88
Why is a measles booster given?
Outbreaks in children <5 y/o are unvaccinated Outbreaks in children 5-18 y/o are vaccinated
89
What are the symtpoms of rubella?
URTI and maculopapular rash
90
How is rubella diagnosed?
Isolation of rubella virus OR significant rise in rubella IgG by any standard serologic assay OR positive serologic test for rubella IgM antibody
91
What is congenital rubella syndrome?
Acute infection of rubella during the first three months of pregnancy can lead to infection of the fetus; if mild and chronic, this develops; if severe, spontaneous abortions and stillbirths occur
92
What are the effects of CRS?
Deafness, cataracts, heart defects, microcephaly, mental retardation, bone alterations, liver and spleen damage
93
What are the structural features of parvovirus B19?
Single-stranded DNA virus with capsid
94
How is parvovirus B19 spread?
Respiratory and oral secretions
95
Discuss the pathogenesis of parvovirus B19.
Infects mitotically active erythroid precursor cells in the bone marrow and establishes lytic infection Initial symptoms are flu-like and due to viral shedding; later phase is related to immune response Can cross the placenta and infect the baby
96
What are the symptoms of parvovirus B19 infection?
Mild, flu-like illness with fever, headache, chills, myalgia, malaise Erythema infectiosum (fifth disease/slapped cheek syndrome) Aplastic crisis in people with chronic anemia Arthropathy (polyarthritis) Risk of fetal loss (can cross the placenta), also causes anemia-related disease, but not congenital anomalies
97
How is parvovirus B19 diagnosed?
Erythema infectiosum - clinical diagnosis Virus specific IgM and/or viral DNA evaluation for other presentations
98
What is the most common manifestation of disease associated with Mumps virus infection?
Parotitis
99
How is the Mumps virus most commonly transmitted?
Respiratory
100
How is Mumps virus currently diagnosed?
Clinical symptoms with confirmation by serology performed by the public health department
101
What is the most common pathogenesis of a Mumps infection?
Viral replication in respiratory tract leading to viremia & infection and inflammation of parotid gland
102
Are there any approved anti-virals against Mumps infection?
No
103
Is there a vaccine currently available for Mumps virus?
Live-attenuated vaccine in combination with Measles and Rubella and Varicella
104
Are there any major consequences to Mumps infections?
Long-term immunity
105
What is the most common manifestation of disease associated with Measles virus infection?
Maculopapular rash, coryza, cough and conjunctivitis and Koplik's spots
106
How is the Measles virus usually transmitted?
Respiratory from the cough of infected person
107
How is Measles virus currently diagnosed?
Clinical symptoms with confirmation by serology performed by the public health department
108
What is the most common pathogenesis of a Measles infection?
Viral replication in respiratory tract leading to viremia and rash
109
Are there any approved anti-virals against Measles infection?
No
110
Is there a vaccine currently available for Measles virus?
Live-attenuated vaccine in combination with Mumps and Rubella and Varicella
111
Are there any major consequences to Measles infections?
Risk of subacute sclerosing panencephalitis
112
What is the most common disease associated with Parainfluenza virus in children?
Croup
113
How is parainfluenza virus transmitted?
Respiratory droplets
114
Wha is the current recommended mode of detection for Parainfluenza virus?
Clinical diagnosis by common presentation and film array RT-PCR
115
Knowing the pathogenesis of Parainfluenza virus, which of the following are the expected clinical findings?
Coldlike symptoms, bronchitis, croup They are not systemic and do NOT cause viremia
116
Are there any effective therapeutic agents available to treat Parainfluenza virus infections?
Glucocorticoids for severe cases of croup
117
Is there a vaccine currently available for Parainfluenza virus?
No
118
Are there any long term complications to Parainfluenza virus infection?
Short-term immunity
119
What is the common name given to Rubella virus infection?
German measles
120
How is the Rubella virus usually transmitted?
Respiratory | Mother to fetus
121
What laboratory test is done to diagnose Rubella virus?
Serology
122
What is the most common pathogenesis of a Rubella infection?
Viral replication in respiratory tract leading to viremia and rash
123
Are there any approved anti-virals against Rubella infection?
No
124
Is there a vaccine currently available for Rubella virus?
Live-attenuated vaccine in combination with Mumps and Measles and Varicella
125
Are there any consequences to Rubella infections in pregnant women?
Congenital rubella syndrome

MHD2 (34 decks)

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