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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
Q

What are some additional common respiratory viruses?

A 
Rhinovirus
Coronavirus
Adenovirus
Influenza
Para-flu and RSV
HSV and EBV
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26
Q

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.

A

True

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27
Q

True or false - Rhinoviruses, Adenoviruses, and Coronaviruses can all cause the common cold.

A

True

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28
Q

Rhinoviruses cause acute infections in the ___. Vaccines are of limited utility - why?

A

Respiratory tract; diversity (hundreds) of serotypes

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29
Q

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.

A

Conjunctivitis; pink eye

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30
Q

Coronaviruses can cause both respiratory and ___ infections. They are common in children and often cause ___.

A

GI; croup

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31
Q

Small changes in the surface glycosylation of the influenza virus are called ___.

A

Camouflage (block antibody binding site)

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32
Q

What is the genome and family of influenza virus?

A

Segmented negative strand RNA orthomyxovirus

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33
Q

How is influenza virus most common transmitted?

A

Respiratory

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34
Q

What is the current method of detection of influenza virus?

A

Film array RT-PCR assay

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35
Q

What is the mechanism of pathogenesis of influenza virus infection

A

Exuberant immune responses cause lethargy, muscle aches, fever while necrotic infected cell debris and inflammatory infiltrates occupy airways and impede breathing

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36
Q

Are there any anti-viral therapies available against influenza virus?

A

Amantidine or Neuraminidase inhibitors (tami-flu)

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37
Q

Are there any vaccines available against influenza virus?

A
  1. Live-attenuated vaccine (flu-mist)

2. Killed virus vaccines with current year HA and NA

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38
Q

Why do people need to be vaccinated annually for influenza virus?

A

Because new influenza strains arise due to antigenic drift and antigenic shift

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39
Q

What causes pandemic influenza virus outbreaks?

A

RNA segment reassortment causing antigenic shift

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40
Q

What are common causes of respiratory infections?

A

Viruses (82%) - rhinovirus, parainfluenza virus, influenza virus, RSV, adenovirus, enterovirus

Bacterial (13%) - GAS

Mycoplasma and other (4%)

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41
Q

When do influenza and RSV present temporally?

A

Winter (peak)

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42
Q

What are the viruses in the paramyxoviridae family?

A
  1. Parainfluenza (types 1-4)
  2. Mumps
  3. Measles
  4. RSV (types A and B)
  5. Metapneumovirus (types A and B)
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43
Q

How does RSV present in infants/young children, adults, and elderly?

A

Infants/young children - LRTI
Adults - milder URTI
Elderly - pneumonia

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44
Q

How is RSV transmitted?

A

Respiratory (generally requires close contact)

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45
Q

What type of patient is at high risk for complications of RSV?

A

Infants who are premature, immunocompromised, or have congenital heart disease

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46
Q

Discuss the pathology of RSV infection.

A

Necrosis of bronchiolar epithelium in 18-24 hours, submucosal edema, bronchioles occluded with mucus and cellular debris, hyperinflation and air trapping

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47
Q

How are respiratory specimens worked up?

A

RT-PCR (1-3 hours, FilmArray Respiratory Panel tests for 20 pathogens)

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48
Q

What is the preventive treatment for RSV in high-risk infants?

A

Palivizumab - humanized Ig - expensive but effective

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49
Q

What is the MOA of Palivizumab?

A

Monoclonal Ab that binds RSV F (fusion) protein, prevents attachment to the cell

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50
Q

What is human metapneumovirus (hMPV)?

A

A new virus that presents similarly to RSV, with a less severe disease outocme

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51
Q

Discuss the features of parainfluenza virus infections.

A

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
Q

How is parainfluenza virus transmitted?

A

Inhalation of large droplet aerosols

53
Q

How does parainfluenza virus infection present in children and adults?

A

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
Q

What is the geographic and seasonal preference of parainfluenza virus?

A

Ubiquitous, worldwide, seasonal

55
Q

Discuss the various presentations of parainfluenza virus.

A

NOT systemic, no viremia

Coldlike symptoms, bronchitis, bronchiolitis, croup (laryngotracheobronchitis)

56
Q

What type of protective immunity develops after infection with parainfluenza?

A

Protective immunity of relatively short duration

57
Q

What is another viral cause of croup?

A

Human coronavirus NL-63

58
Q

Which type of parainfluenza virus is most common?

A

Type 3

59
Q

What are the genomic features of paramyxoviridae viruses?

A

Negative single strand RNA viruses that induce cell fusion (syncytium formation)

60
Q

How does RSV appear in tissue culture?

A

Syncytia - amalgamation of cells with the loss of cell border, multinucleated cells, intracytoplasmic inclusions

61
Q

Of the 4 major types of paramyxoviruses (parainfluenza, mumps, measles, RSV), which have fusion proteins?

A

All

62
Q

Of the 4 major types of paramyxoviruses (parainfluenza, mumps, measles, RSV), which have hemagglutinin?

A

Parainfluenza
Mumps
Measles

(NOT RSV)

63
Q

Of the 4 major types of paramyxoviruses (parainfluenza, mumps, measles, RSV), which have neuraminidase?

A

Parainfluenza
Mumps

(NOT measles or RSV)

64
Q

Of the 4 major types of paramyxoviruses (parainfluenza, mumps, measles, RSV), what type of immunity develops for each?

A

Short-lived - parainfluenza, RSV

Life-long - mumps, measles

65
Q

Of the 4 major types of paramyxoviruses (parainfluenza, mumps, measles, RSV), which have multiple antigenic types?

A

Parainfluenza - 4

RSV - 2

66
Q

Of the 4 major types of paramyxoviruses (parainfluenza, mumps, measles, RSV), which have a vaccine?

A

Mumps and measles (both live-attenuated)

RSV - in development

67
Q

What is the most common disease associated with RSV?

A

Severe lower respiratory tract infection in children

68
Q

How is RSV usually transmitted?

A

Inhalation of respiratory droplets

69
Q

What is the current recommended mode of detection for RSV?

A

Film array RT-PCR of nasal wash

70
Q

What is the pathogenesis of RSV?

A

Necrosis of bronchiolar epithelium in 18-24 hours, submucosal edema, bronchioles occluded with mucosa and cellular debris, and hyperinflation and air trapping

71
Q

Are there any effective anti-viral agents available for treatment of hospitalized children with RSV?

A

No

72
Q

Are there any effective therapeutics against RSV?

A

Administer Palivizumab prior to infection

73
Q

Is there a vaccine currently available for RSV?

A

No

74
Q

Are there any long-term consequences to RSV infections?

A

Less severe reinfection and short-term immunity

75
Q

How is mumps transmitted?

A

Respiratory droplets

76
Q

Discuss the pathogenesis of mumps virus.

A

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
Q

What is the incubation period of mumps infection?

A

7-14 days

78
Q

What is the classic symptom of mumps?

A

Swelling of parotid glands

79
Q

What component of host defense is necessary to combat mumps?

A

CMI (Ab is not sufficient due to mumps’ ability to spread cell to cell)

Note - CMI is partly responsible for symptoms

80
Q

What is the clinical definition of mumps?

A

Acute onset of unilateral or bilateral swelling of the parotid or salivary gland lasting >2 days without another apparent cause

81
Q

What is the lab criteria for diagnosis of mumps?

A

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
Q

Describe the features of the mumps vaccine.

A

Live-attenuated, 95% effective, lifelong immunity, 1 dose + 1 boost, administered with MMRV

83
Q

What is a leading cause of vaccine-preventable deaths in children?

A

Measles

84
Q

What are the symptoms of measles?

A

Characteristic maculopapular rash, coryza, cough, conjunctivitis, Koplik’s spots (grain-of-salt appearance in mouth)

85
Q

What are possible complications of measles?

A

Diarrhea, oitis media, croup, bronchopneumonia, encephalitis and subacute sclerosing panencephalitis

86
Q

What is the incubation period of measles?

A

~7 days

87
Q

What is the course of measles?

A

7 day incubation period
~1 week of viremia, viriuria, viral shedding
Rash presents between day 10-14

88
Q

Why is a measles booster given?

A

Outbreaks in children <5 y/o are unvaccinated

Outbreaks in children 5-18 y/o are vaccinated

89
Q

What are the symtpoms of rubella?

A

URTI and maculopapular rash

90
Q

How is rubella diagnosed?

A

Isolation of rubella virus OR significant rise in rubella IgG by any standard serologic assay OR positive serologic test for rubella IgM antibody

91
Q

What is congenital rubella syndrome?

A

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
Q

What are the effects of CRS?

A

Deafness, cataracts, heart defects, microcephaly, mental retardation, bone alterations, liver and spleen damage

93
Q

What are the structural features of parvovirus B19?

A

Single-stranded DNA virus with capsid

94
Q

How is parvovirus B19 spread?

A

Respiratory and oral secretions

95
Q

Discuss the pathogenesis of parvovirus B19.

A

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
Q

What are the symptoms of parvovirus B19 infection?

A

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
Q

How is parvovirus B19 diagnosed?

A

Erythema infectiosum - clinical diagnosis

Virus specific IgM and/or viral DNA evaluation for other presentations

98
Q

What is the most common manifestation of disease associated with Mumps virus infection?

A

Parotitis

99
Q

How is the Mumps virus most commonly transmitted?

A

Respiratory

100
Q

How is Mumps virus currently diagnosed?

A

Clinical symptoms with confirmation by serology performed by the public health department

101
Q

What is the most common pathogenesis of a Mumps infection?

A

Viral replication in respiratory tract leading to viremia & infection and inflammation of parotid gland

102
Q

Are there any approved anti-virals against Mumps infection?

A

No

103
Q

Is there a vaccine currently available for Mumps virus?

A

Live-attenuated vaccine in combination with Measles and Rubella and Varicella

104
Q

Are there any major consequences to Mumps infections?

A

Long-term immunity

105
Q

What is the most common manifestation of disease associated with Measles virus infection?

A

Maculopapular rash, coryza, cough and conjunctivitis and Koplik’s spots

106
Q

How is the Measles virus usually transmitted?

A

Respiratory from the cough of infected person

107
Q

How is Measles virus currently diagnosed?

A

Clinical symptoms with confirmation by serology performed by the public health department

108
Q

What is the most common pathogenesis of a Measles infection?

A

Viral replication in respiratory tract leading to viremia and rash

109
Q

Are there any approved anti-virals against Measles infection?

A

No

110
Q

Is there a vaccine currently available for Measles virus?

A

Live-attenuated vaccine in combination with Mumps and Rubella and Varicella

111
Q

Are there any major consequences to Measles infections?

A

Risk of subacute sclerosing panencephalitis

112
Q

What is the most common disease associated with Parainfluenza virus in children?

A

Croup

113
Q

How is parainfluenza virus transmitted?

A

Respiratory droplets

114
Q

Wha is the current recommended mode of detection for Parainfluenza virus?

A

Clinical diagnosis by common presentation and film array RT-PCR

115
Q

Knowing the pathogenesis of Parainfluenza virus, which of the following are the expected clinical findings?

A

Coldlike symptoms, bronchitis, croup

They are not systemic and do NOT cause viremia

116
Q

Are there any effective therapeutic agents available to treat Parainfluenza virus infections?

A

Glucocorticoids for severe cases of croup

117
Q

Is there a vaccine currently available for Parainfluenza virus?

A

No

118
Q

Are there any long term complications to Parainfluenza virus infection?

A

Short-term immunity

119
Q

What is the common name given to Rubella virus infection?

A

German measles

120
Q

How is the Rubella virus usually transmitted?

A

Respiratory

Mother to fetus

121
Q

What laboratory test is done to diagnose Rubella virus?

A

Serology

122
Q

What is the most common pathogenesis of a Rubella infection?

A

Viral replication in respiratory tract leading to viremia and rash

123
Q

Are there any approved anti-virals against Rubella infection?

A

No

124
Q

Is there a vaccine currently available for Rubella virus?

A

Live-attenuated vaccine in combination with Mumps and Measles and Varicella

125
Q

Are there any consequences to Rubella infections in pregnant women?

A

Congenital rubella syndrome

MHD2 (34 decks)

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