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2. HDS Pulmonary > Viral Respiratory Pathogens > Flashcards

Viral Respiratory Pathogens Flashcards

1
Q

Respiratory Viruses

Categories

A
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2
Q

Viral Respiratory Infections

Overview

A
  • Viruses cause 75-80% of respiratory infections
  • Greatest incidence in young children
  • Each virus targets certain age groups & certain parts of respiratory tract
  • One virus ⇒ many disease syndromes
  • One syndrome ⇒ many viral causes
  • Severity ranges
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3
Q

Viruses by Location

A
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4
Q

Viruses by Syndrome

A
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5
Q

Common Cold

Characteristics

A
  • Most common viral pathogens
    • Rhinovirus
    • Parainfluenza
    • RSV
    • Adenovirus
    • Coronavirus
  • Seasonal variations in peak incidence
  • Spread via respiratory secretions
  • Enters RT as aerosolized droplets
    • Larger droplets ⇒ nose
    • Smaller droplets ⇒ airways or alveoli
  • Generally 1-4 day incubation period
  • Adults ⇒ 2-3 colds / yr
  • Kids ⇒ 8-12 colds / yr
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6
Q

Common Cold

Syndromes

A
  • Rhinitis ⇒ inflammation of nasal mucosa
  • Sinusitis ⇒ inflammation of sinus mucosa
  • Pharyngitis ⇒ inflammation of pharynx and throat
  • Conjunctivitis
  • Otitis media
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7
Q

Common Cold

Symptoms

A
  • Headache
  • Nasal discharge and congestion
  • Cough
  • Coryza ⇒ catarrhal inflammation of the mucous membranes in nose, caused esp. by a cold or by hay fever.
  • Fever
  • N/V
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8
Q

Common Cold

Severity

A
  • Most are acute, relatively mild, self-limited
  • Severe illness in infants, elderly, chronically ill, and immunocompromised
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9
Q

Common Cold

Complications

A

Mostly secondary bacterial infections.

See otitis media, sinusitis, or PNA.

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10
Q

LRT

Viral Infections

A
  • Influenza and RSV most common
  • Incubation ⇒ 1-4 days
  • Communicable
    • Respiratory droplets
    • Direct transmission via fomites
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11
Q

Viral Respiratory Infection

Pathogenesis

A
  • Entry via URT including nose and eyes
    • Viral inoculum ∝ pathogenesis
  • Infection occurs in respiratory epithelium
    • ± Airway cell destruction
    • ± Epithelial denuding
    • ± Ciliary compromise
  • Normal clearance impaired
  • ± Interaction w/ immune system
    • ∆ Phagocytic cell function
    • Promote immediate hypersensitivity reactions
      • Virus-induced wheezing and asthma
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12
Q

Seasonality

A

Each virus predominants during a certain time period with overlap.

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13
Q

Viral Immunity

A
  • Cytotoxic CD8+ T-cells
    • Major role in combating current infection
    • Long-lived memory T cells
  • Secretory IgA ⇒ important for URT
  • Circulating IgG ⇒ important for LRT
  • Immunity may be transient and partially protective
  • Multiple serotypes ⇒ “new” infection each time
  • Antigenic variants of recirculating viruses ⇒ immunity not completely cross-protective
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14
Q

Rhinovirus

Characteristics

A
  • Picornavirus family
  • Enterovirus genus
  • Non-enveloped
  • Non-segmented ⊕-sense ssRNA virus
  • Acid labile
  • Antigenic diversity ⇒ > 100 serotypes
    • Circulates simultaneously but most prevalent types change yearly
  • Ab to ~ 50% of serotypes by adulthood
  • Infection ⇒ lasting type-specific immunity
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15
Q

Rhinovirus

Lifecycle

A
  • Binds cellular receptor ⇒ species barrier
    • ICAM-1 ⇒ 90%
    • VLDL receptor ⇒ 10%
  • Entirely cytoplasmic
  • Infectious only to humans and chimpanzees
  • Replication most efficient @ 33°C
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16
Q

Rhinovirus

Clinical Features

A
  • Transmitted via respiratory aerosols or fomites
    • Viral load ∝ sx severity
  • Incubation ⇒ 2-5 days
  • Symptoms ⇒ 3-7 days
  • Viral shedding ⇒ up to 3 weeks
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17
Q

Rhinovirus

Pathogenesis

A
  • 1° site @ epithelial surface of nasal mucosa
  • Minimal direct virus-induced cell damage
  • Majority of sx immunogenic
    • Nose becomes inflamed and hyperemic
    • Discharge becomes mucopurulent w/ many PMNs
  • Primary sx generally mild
    • Rhinorrhea
    • ST
    • Minimal cough
    • Low grade fever
  • Can induce COPD and asthma exacerbations
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18
Q

Rhinovirus

Epidemiology

A
  • Most frequent cause of common cold in adults
    • ⅓ to ½ of cases
  • Major cause of common cold in children
    • Major reservoir
  • Peak activity in fall and spring
  • 3-4 serotypes abundant at a time
    • Rhinovirus A and B ⇒ URTI
    • Rhinovirus C ⇒ LRTI
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19
Q

Rhinovirus

Immunity

A
  • Infection ⇒ serotype-specific immunity
  • Primarily due to nasal sIgA
  • Cytotoxic T-cells also very important
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20
Q

Rhinovirus

Dx, Tx, and Prevention

A
  • Clinical dx
  • Symptomatic tx w/ supportive care
    • No abx
  • Vaccine development unlikely
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21
Q

Coronavirus

Characteristics

A
  • Enveloped, helical nucleocapsid
    • Contains large, widely spaced, crown-like spikes
    • S and M glycoproteins
  • Linear, non-segmented, ⊕-sense ssRNA
  • Only 2 serotypes in humans
  • Can undergo rapid genetic change
    • Alterations in clinical disease
    • “Trans-species” movement to new hosts
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22
Q

Coronavirus

Envelope

A
  • S glycoprotein (spike)
    • Large crown-like surface projections
    • Receptor binding
    • Cell fusion
    • Major antigen
  • M glycoprotein (membrane)
    • Transmembrane
    • Packaging and budding
    • Envelop formation
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23
Q

Coronavirus

Clinical Features

A
  • Incubation ⇒ 2-3 days
  • Symptoms ⇒ 3 days
  • Viral shedding ⇒ 1-4 days
  • Little or no systemic immunity
  • Local immunity lasts 1-2 years
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24
Q

Coronavirus

Replication

A
  • Viral encoded RNA-dependent RNA polymerase
  • Nested subgenomic mRNA transcribed from ssRNA
    • One protein translated from each message
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25
Q

Coronavirus

Transmission

A
  • Aerosols of respiratory secretions
  • Direct transmission via fomites
  • Fecal-oral transmission rare
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26
Q

Coronavirus

Epidemiology

A
  • Accounts for 10-30% of all colds
    • Usually in URT
    • LRT disease used to be uncommon
  • Fewer infections in children than rhinoviruses
  • Young children most likely infected
  • Most people infected w/ 1+ common coronaviruses in lifetime
  • Winter and spring seasonality
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27
Q

Coronavirus

Symptoms

A
  • Common cold sx
    • Rhinorrhea
    • Coughing
    • Sore throat
    • Headache
    • Fever
  • Can sometimes cause LRTI ⇒ bronchitis or PNA
    • People w/ cardiopulmonary disease
    • Immunocompromised
    • Infants
    • Elderly
  • Gastroenteritis in infants
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28
Q

Coronavirus

Dx, Tx, and Prevention

A
  • Diagnosis
    • Clinical suspicion for common human coronavirus
    • Serology for complicated/novel cases
      • MERS, SARS, COVID-19
  • Treatment
    • Symptomatic
    • No abx
  • Prevention
    • Currently no vaccine
    • Wash hands
    • Avoid touching face
    • Avoid close contact with sick people
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29
Q

SARS

Overview

A

Severe Acute Respiratory Syndrome

  • Caused by SARS-CoV-1
  • Mortality 3-6%
    • 45-63% in persons > 60 y/o
  • Severe viral PNA
  • Associated Coronavirus SARS-HCoV
  • Incubation ⇒ 2-7 days
  • Greatest transmission around 10th day
    • When person is sickest ⇒ easy to isolate
  • Began with bats ⇒ Civet cats ⇒ humans
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30
Q

SARS

Symptoms

A
  • High fever (usu. > 100.4 F)
  • Headache
  • Mild respiratory sx
  • Myalgia
  • Fatigue
  • Diarrhea ⇒ 10-20%
  • Non-productive cough ⇒ day 2-7
  • Chills
  • Dizziness
  • Many pts develop PNA
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31
Q

SARS

Diagnosis

A
  • PCR of two sites or two different times
  • ELISA test for Ab
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32
Q

MERS

Overview

A

Middle East Respiratory Syndrome

  • Caused by MERS-CoV
    • Distinct from other coronavirus
    • Most similar to those found in bats
    • Also found in camels
  • Transmission mode unclear
    • Few primary cases with direct camel contact
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33
Q

MERS

Clinical Presentation

A
  • Range of presentations
    • 62% severe respiratory illness
    • 5% mild sx
    • 21% asymptomatic
  • Data from early cases
    • High mortality
    • LRTI, fever
  • Data from more recent cases
    • Lower mortality
    • Higher proportion w/ URTI
  • No vaccine, no specific treatment
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34
Q

MERS

Symptoms

A
  • Fever > 38°C or 100.4°F
  • Cough
  • SOB
  • Malaise
  • Vomiting
  • Diarrhea
  • PNA
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35
Q

MERS

Transmission and Epidemiology

A
  • 65% male
  • Age ranges 9 m/o to 94 y/o
    • Median 49 y/o
    • Mean 56 y/o
  • Infectious period unclear
    • Not believed to be contagious before sx onset
  • ~75% identified as “secondary”
    • Mostly healthcare workers ⇒ 19%
    • Many with little or no sx
  • Many clusters
  • No sustained person-to-person transmission
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36
Q

COVID-19

Overview

A

Coronavirus disease 2019

  • Caused by SARS-CoV2
  • Incubation ⇒ 2-14 days
    • Median 4-5 days
  • ↑ Risk of severe illness in specific populations
    • Cardiopulmonary disease, DM, immunodeficiency
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37
Q

COVID-19

Transmission

A
  • Transmits easier from person-to-person
    • Droplet
    • Aerosol
    • Contact/fomites
    • ? Fecal-oral route
  • Transmits easily when sx early or pt asymptomatic
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38
Q

COVID-19

Clinical Presentation

A
  • Most common sx
    • Fever
    • Cough
    • SOB
  • Other sx
    • Sore throat
    • Runny or stuffy nose
    • Body aches
    • Headache
    • Chills
    • Fatigue
    • Nausea and diarrhea
    • Loss of taste and smell
    • Myocarditis demonstrated in asymptomatic pts
  • Elderly w/ higher rates of severe illness
  • Children and younger adults w/ less severe illness and less death
  • ? Effect on pregnant women and fetus
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39
Q

COVID-19

Testing

A
  • PCR from anterior nasal swab
  • ELISA test for Ab
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40
Q

Novel Coronaviruses

Comparison

A
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41
Q

Adenovirus

Characteristics

A
  • Family ⇒ Adenoviridae
  • Large, non-enveloped, icosadeltahedron virions
  • Linear dsDNA ass. w/ ⊕-charged protein core
  • ~50 Ag distinct serotypes in 6 subgenera ⇒ A-F
  • Adenovirus types 1-7 most common
42
Q

Adenovirus

Capsid Structure

A
  • Capsid made of 240 capsomeres
    • Consists of hexons and pentons
  • Fiber proteins project from capsid
    • Contains viral attachment proteins
    • Can act as hemagglutinin
    • Determine target cell specificity
  • Pentons and fibers also carry type-specific Ag
43
Q

Adenovirus

Clinical Features

A
  • Incubation ⇒ 5-10 days
  • Sx duration ⇒ 1-2 weeks
  • Viral shedding ⇒ several months up to years
  • Infections are very common and mostly asymptomatic
    • Most ppl infected with at least one type by age 15
  • Affects respiratory, GI, and eyes
  • Oncogenic potential in animals
44
Q

Advenovirus

Transmission

A
  • Methods:
    • Respiratory droplets
    • Fecal-oral contact
    • Fingers
    • Fomites (including towels and medical instruments)
    • Poorly chlorinated swimming pools
  • Resistant to:
    • Drying
    • Detergents
    • GI tract secretions (acid, protease, bile)
    • Mild chlorine treatment
  • Close interactions promotes viral spread
    • Classrooms, military barracks
  • Asymptomatic infections also faciliate spread
45
Q

Advenovirus

Pathogenesis

A
  • Initial site of replication likely oropharynx or eye
  • Local infection ⇒ ± viremia ⇒ ± systemic spread to visceral organs
  • Destruction of infected cells & immune response ⇒ host injury
  • Transmitted via lungs, OP, and stool
46
Q

Adenovirus

Clinical Syndromes

A
  • Infects children > adults
  • Clinical syndromes typically involve respiratory tract, GI tract, or eyes
    • Respiratory tract infections
    • PNA
    • Conjunctivitis
    • Hemorrhagic cystitis
    • Gastroenteritis
  • Affects respiratory and GI tract equally
  • Sx vary depending on strain
  • Most recover but mortality possible
  • Reactivation has been documented
    • Can persist in host lymphoid tissue for years
    • Occurs in immunocompromised ppts
47
Q

Swimming Pool

Adenovirus

A

“Swimming pool conjunctivitis”

  • Mild follicular conjunctivitis
    • Mucosa of palpebral conjunctiva becomes nodular
  • Caused by adenoviruses d/t chlorine resistance
  • Transmission in contaminated swimming pools
  • Risk factors ⇒ irritation of eye by FB, dust, or debris
48
Q

Adenovirus

Diagnosis

A
  • Immunoassays
    • Fluorescent Ab
    • Enzyme-linked immunosorbent assays
  • PCR
    • Detect & type virus in clinical samples
  • Serological assays
    • CFA, HI, EIA
    • Neutralization techniques
    • Rarely used
49
Q

Adenovirus

Treatment and Prevention

A
  • Treatment
    • No specific antiviral therapy
    • Given supportive care
  • Prevention
    • Vaccine against ARDS
    • Consists of live adenovirus 4, 7, and 21
    • Enterically coated capsules
    • Given to new recruits in the military
50
Q

Parainfluenza virus

Characteristics

A
  • Family ⇒ Paramyxoviridae
    • Closely related to Mumps virus
  • Enveloped ⊖-sense ssRNA virus
  • Pleomorphic morphology
  • Replicates in cytoplasm
  • 5 serotypes ⇒ 1, 2, 3, 4a, and 4b
    • Distinguished by Ag, cytopathic effect, and pathogenesis
51
Q

Parainfluenza

Structure

A
  • Linear nucleocapsid
  • Envelop contains
    • Hemagglutinin/neuraminidase
    • Fusion F protein
52
Q

Parainfluenza

Clinical Features

A
  • Incubation ⇒ 3-6 days
  • Sx duration ⇒ 7-10 days
  • Viral shedding ⇒ 1 week
  • Replication limited to respiratory epithelial cells
  • Serious problem in infants and small children
  • Infection becomes milder as child ages
53
Q

Parainfluenza

Transmission

A
  • Direct person-to-person contact
  • Large droplet aerosols
    • Infectious for > 1 hour
54
Q

Parainfluenza

Clinical Syndromes

A
  • Croup (laryngotracheobronchitis)
    • Most common manifestation
    • Caused mostly by HPIV-1 and sometimes -2
    • Other viruses may cause croup e.g. flu and RSV
  • Bronchiolitis ⇒ mostly HPIV-3
  • PNA ⇒ mostly HPIV-3
  • Flu-like tracheobronchitis
  • Coryza-like illnesses
55
Q

Parainfluenza

Pathogenesis

A
  • Viruses multiply throughout tracheobronchial tree
  • Induces production of mucus
  • Vocal cords of larynx become grossly swollen
    • Obstructs inflow of air ⇒ inspiratory stridor
56
Q

Parainfluenza

Genetics

A

Parainfluenza more genetically stable than influenza virus:

Very little mutation

Minimal antigenic drift

No antigenic shift

57
Q

Parainfluenza

Immunity

A
  • Only transient immunity to infection
  • Maternal Ab not protective for infants
  • Secretory IgA protects against reinfection ⇒ short-lived
  • F protein Ab’s
    • Neutralize infectivity
    • Prevent cell-to-cell spread
  • HN protein Ab’s
    • Only neutralize infectivity
58
Q

Parainfluenza

Dx, Tx, Prevention

A
  • Diagnosis
    • Rapid test by Ag detection from nasopharyngeal aspirates and throat washings
    • Viral isolation
    • Serology
      • Retrospective dx
      • CFT most widely used
  • Treatment
    • No specific antivrals
    • Severe croup hospitalized and placed in oxygen tents
  • No vaccine available
59
Q

Influenza

Characteristics

A
  • Family ⇒ Orthomyxoviridae
  • Enveloped virus
    • Spikes extend from envelope ⇒ major Ag
  • Segmented ⊖-sense ssRNA
  • 3 types ⇒ Influenza A, B, C
60
Q

Influenza

Envelop Structure

A

Spikes extend from envelope.

Act as major antigens.

Type A & B ⇒ hemagglutinin & neuraminidase

Type C ⇒ hemagglutinin only

  • Hemagglutinin
    • Bind to cellular receptors containing sialic acid
  • Neuraminidase
    • Important in release of virus from infected cells
61
Q

Influenza

Genome

A

Segmented ⊖sense ssRNA

  • Flu A & B
    • 8 viral RNA segments
    • Codes for 10 proteins
  • Flu C
    • 7 viral RNA segments
    • Codes for 8 proteins
  • Total genome ~ 12-15K nucleotides
  • First 12-13 nucleotides conserved among all RNA segments
62
Q

Influenza

Genetic Changes

A
  • Flu A ⇒ antigenic shift and drift
  • Flu B ⇒ antigenic drift only
  • Flu C ⇒ relatively stable
63
Q

Influenza

Classification

A
  • Type ⇒ A, B, or C
    • Based on ribonucleoprotein (NP)
  • Strain (Serotypes or Subtypes)
    • Based on hemagglutinin (H) and neuraminidase (N)
    • Immunologically distinct hemagglutinin subtypes ⇒ 16H, 9N
    • Common infections in humans ⇒ H1, H2, H3; N1, N2
    • “Emerging” ⇒ H5 and H6
64
Q

Influenza

Nomenclature

A

Designated by:

  1. Type
  2. Geographic origin
  3. Strain number
  4. Year of isolation
  5. Description of hemagglutinin and neuraminidase

Type/Geo/Strain no./Year/H,N

Ex. A/Hong Kong/03/68/(H3N2)

Ex. A/New Jersey/9/1976/(H1N1)

Ex. A/swine/Iowa/15/30(H1N1)

65
Q

Influenza

Clinical Features

A
  • Upper and/or lower respiratory tract
  • Primarily in cilicated epithelial cells
  • Incubation ⇒ 18-96 hours (~ 2 days)
  • Duration of disease ⇒ 2-5 days
  • Highly contagious ⇒ begins 1 day prior to onset of infection, lasts 4-5 days
  • Infections ⇒ sporadic, local outbreak, widespread epidemics
  • Usually causes a mild febrile illness
  • Epidemics
    • Northern hemisphere ⇒ winter months
    • Southern hemisphere ⇒ May-Sept
66
Q

Influenza

Transmission

A
  • Aerosol ⇒ coughing or sneezing
    • 100k - 1 mil virons per droplet
  • Shedding
    • Touching an infected person or an item contaminated with the virus then touching your eyes, nose, or mouth
    • Able to infect others 1 day before sx appear and up to 7 days after
67
Q

Influenza

Symptoms

A

Presentations can vary

  • Fever
  • Headache
  • Extreme tiredness
  • Dry cough
  • Sore throat
  • Runny or stuffy nose
  • Muscle aches
  • GI sx ⇒ N/V/D
    • More common in kids > adults
68
Q

Influenza

Complications

A
  • PNA ⇒ viral and bacterial
  • Croup
  • Asthma
  • Bronchitis
  • Myocarditis and pericarditis
  • Death
69
Q

Influenza

Pathogenesis

A
  • Inoculation via respiratory aerosols or fomites
  • Few respiratory epithelial cells infected if:
    • Avoid removal by cough reflex
    • Escape neutralization by sIgA
    • Avoid inactivation by nonspecific inhibitors in mucous secretions
  • Replication and spread to adjacent cells
  • Viral NA protein ⇒ ↓ viscosity of mucus ⇒ uncovers cellular surface receptors ⇒ promote spread of virus-containing fluid to LRT
70
Q

Influenza

Immunity

A
  • IFN-𝛾 ⇒ limits spread of disease
  • Cytotoxic T-cells ⇒ limit shed of virus by killing infected cells
  • Ab ⇒ induced and limits subsequent infections
71
Q

Influenza

Epidemiology

A
  • 0.5-1 mil deaths/yr worldwide
    • 36k in US
    • 200k hospitalizations in US
    • 5-20% infected in US
  • 3 pandemics of 20th century
    • 1918 Spanish flu
      • H1N1 strain
      • Killed up to 100 million
    • 1957 Asian flu
      • H2N2 strain
      • Killed 70k in US
      • Killed > 1 mil worldwide
    • 1968 Hong Kong flu
      • H3N2 strain
      • Killed 34k in US
  • Billion $ economic cost associated
72
Q

Influenza

Diagnosis

A
  • Rapid Diagnosis
    • NP, throat, or nasal swabs
    • Ag detection ⇒ IFA or EIA
    • RNA detection ⇒ RT-PCR
      • Best sensitivity and specificity
      • Expensive and technically demanding
  • Virus isolation
  • Serology
    • Retrospective dx
    • CFT most widely used
    • HAI and EIA may be used for type-specific dx
73
Q

Influenza

Treatment

A
  • M2 ion channel blockers
    • Amantidine & Rimantadine
    • ⊗ M2 ⇒ ⊗ H+ ion flow ⇒ ⊗ viral replication
    • Drop in pH needed for viral uncoating
    • Adverse neurological and GI effects
    • Rapid emergence of resistant strains
    • 2011 – no longer recommended by CDC to treat or prevent Flu A
  • Neuraminidase inhibitors
    • Zanamivir (Relenza) & Oseltamivir (Tamiflu) & Peramivir (Rapivab)
    • ⊗ Release of virions from infected cells
      • Virions aggregate @ cell surface
    • ⊗ Spread of infection
    • No or minor AEs
    • Broadly active against all Flu A and Flu B
74
Q

Influenza

Prevention

A
  • Trivalent vaccine ⇒ 2 Flu A & 1 Flu B
  • Quadvalent vaccine ⇒ 2 Flu A & 2 Flu B
  • IM or SubQ injection
  • Grown in eggs
    • Newer vaccines grown in cell culture
  • Must be updated yearly through prediction based on WHO surveillance
  • Success of vaccine based on:
    • Ag matching of prediction strain & circulating strain
    • Age of recipient
    • Previous vaccinations and flu exposure
75
Q

“Flu Shot”

A
  • Inactivated killed virus vaccine
    • Whole virus
    • Subvirion
    • Surface Ag preparations
  • Given IM > intradermal
  • Approved for > 6 m/o
    • Healthy or w/ chronic medical conditions
76
Q

Live Attenuated Influenza Vaccine

(LAIV)

A
  • Live attenuated viruses
    • Strains are cold adapted, temperature sensitive, weakened
  • Induce secretory and systemic immune response
    • Mimic natural infection
  • Contains genes encoding HA & NA of WT virus & 6 remaining internal segments
  • Approved for healthy people age 2-49
    • No pregnant women
  • Intranasal administration
  • 78-100% effective
  • No severe side effects
77
Q

Influenza

Pandemics

A

Occur when new avian flu strains gain ability to infect people and easily spread from person-to-person.

Can occur in two ways:

  1. Reassortment
    • Exchange of seasonal and avian influenza genes in person or pig infected with both strains
  2. Mutation
    • Avian strain becomes more transmissible through adaptive mutation of the virus during human avian influenza infection
78
Q

Antigenic Drift

A
  • Point mutations accumulate ⇒ ∆ AA in protein
  • Immune system selects for advantagous ∆
    • Does not cause variation
  • Need ≥ 2 mutations before new epidemiologically significant strain emerges
79
Q

Antigenic Shift

A
  • Drastic ∆ in HA or NA too big to be caused by mutation
  • Occurs by reassortment
    • Genetic segments from 2 different flu viruses infecting the same cell swap genetic segments
  • Suspect migratory birds infecting domestic birds
  • Pig then infected by both
  • Exchange occurs w/ new avian strain but can still work in the pig
  • Only in Flu A
80
Q

Respiratory Syncytial Virus (RSV)

Characteristics

A
  • Family ⇒ Paramyxovirus
  • Genus ⇒ Pneumovirus
  • Enveloped but no HA or NA
  • Non-segmented ⊖-sense ssRNA virus
  • Subgroups A and B by monoclonal sera
    • Both circulate
  • Causes sizable epidemic each year
81
Q

RSV

Virulence Factors

A

Envelop contains G protein and F protein.

  • G protein
    • Attachment protein
    • Receptor binding ⇒ unknown target
    • Group determinant
  • F protein
    • Fusion protein
    • Promotes virus-cell and cell-cell fusion
    • Candidate vaccine target
    • Target for palivizumab (Synagis)
      • Preventative mAb
82
Q

RSV

Clinical Features

A
  • Incubation ⇒ 4-6 days
  • Duration ⇒ 2-8 days, up to 3 weeks
  • Shedding ⇒ 3-8 days
    • Infants & immunocompromised can shed for up to 4 wks
  • Most common cause of severe LRT infections in infants
    • 50-90% of Bronchiolitis
    • 5-40% of Bronchopneumonia
  • Causes 10% of Croup
  • Sx mild in older children and adults
83
Q

RSV

Transmission

A
  • Aerosol ⇒ sneezing
  • Direct transmisson ⇒ fomites, contagious secretions
  • Highly infectious and ubiquitious
    • ~100% of children infected by 2 y/o
84
Q

RSV

Symptoms

A

Primary sx (mild to severe):

  • URI ⇒ rhinorrhea, ST, minimal cough, low grade fever
  • Bronchitis ⇒ cough
  • Bronchiolitis ⇒ wheezing, SOB
  • PNA ⇒ severe SOB, tachypnea, hypoxemia

High risk groups for complications:

  • Premature infants
  • Cardiopulmonary disease
  • Immunocompromised
85
Q

RSV

At-Risk Infants

A
  • Infants w/ congenital heart disease
    • Worse if hospitalized within first few days of life
  • Infants w/ underlying pulmonary disease
    • Esp. bronchopulmonary dysplasia
    • Can develop prolonged infections w/ RSV
  • Immunocompromised infants
    • May develop LRT disease at any age
86
Q

RSV

Pathogenesis

A
  • Highly infectious, transmits via respiratory secretions
  • 1° multiplication in epithelial cells of URT ⇒ mild illness
  • In ~50% of children < 8 m/o, goes to LRT ⇒ bronchitis, PNA, croup
    • ? Contribution to SIDS and asthma
  • Extensive direct virus-induced damage
    • Primarily epithelial cells of LRT
  • Intense inflammatory response
    • Skewed Th2-like response
    • Induces only partially effective immunity
  • Hallmark of RSV infection is bronchiolitis
87
Q

RSV

Diagnosis

A
  1. Detection of Ag
    • Rapid dx via RSV Ag from NP aspirates
    • Important b/c of available therapy
  2. Virus isolation
    • Readily isolated from NP aspirates
    • Takes several days
  3. Serology
    • Retrospective dx
    • CFT most widely used
88
Q

RSV

Treatment

A
  1. Symptomatic
  2. Aerosolized ribavarin
    • Used for infants w/ severe infection
    • Used for those at risk of severe disease
    • ? Utility
89
Q

RSV

Prevention

A
  • Passive immunization ⇒ Palivizumab (Synagis)
    • Expensive
  • Live attenuated vaccine
    • Under development
    • Deaths associated w/ inactivated vaccine in 1960’s
90
Q

RSV

Immunoprophylaxis

A

Immunoprophylaxis for high risk infants < 24 m/o

Both shown to ↓ hospitalization for any respiratory cause by 50%.

  • RSV-IGIV
    • Pooled polyclonal hyperimmune globulin from selected donors
  • Palivizumab
    • Humanized murine mAb directed against F protein
    • Given IM
91
Q

Mumps Virus

Characteristics

A

“Mumps”

  • Paramyxovirus genus
  • Rubulavirus family
  • Pleomorphic, enveloped virus w/ helical nucleocapsid
  • ⊖-sense ss-RNA
  • Only one mumps serotype
  • Humans are the only natural host
92
Q

Mumps Virus

Envelope Structure

A

Two glycoprotein spikes:

  1. HN
    • Has both hemagglutinin & neuraminidase activity
  2. Fusion protein
    • Enables virus to form multinucleated giant cells by fusing infected cells together
93
Q

Mumps

Clinical Features

A
  • Highly contagious, infectious childhood disease
  • Can occur any time w/ ↑ incidence during late winter to early spring
  • Incubation ⇒ 16-18 days
    • Can arise 12-25 days after exposure
  • Infectious period ⇒ 3 days before - 4 days after active parotitis
  • Prodromal period ⇒ can last 3-5 days
    • Moderate fever, malaise, pain on chewing or swallowing esp. w/ acidic liquids
  • After prodrome, clinical path depends on organ affected
  • Parotitis ⇒ most common
    • Caused by direct viral infection of the ductal epithelium
    • See localized gland inflammation & swelling in front of the ear
  • Other sites
    • CNS
    • Eyes
    • Pancreas
    • Kidneys
    • Testes
    • Ovaries
    • Joints
94
Q

Mumps Virus

Transmission

A

Airborne virus

  • Tiny respiratory droplets w/ coughing or sneezing
  • Direct contact w/ saliva
  • Can occur several days before onset of swelling to 9 days after
  • After entry, travels to back of throat, nose, and cervical lymph glands
95
Q

Mumps

Symptoms

A
  • Sore throat
  • Fever
  • Tiredness
  • Muscle and body aches
  • Loss of appetite
  • Chills
  • Pain w/ chewing or swallowing
  • Salivary gland swelling
96
Q

Mumps

Pathogenesis

A
  • Causes inflammation of salivary glands
    • Parotid glands most common
  • Symptomatic in 20-30% of persons
  • Adults more severely affected vs children
  • Lifelong immunity s/p clinical or subclinical infection
    • Second infections have been documented
97
Q

Mumps

Complications

A
  • Aseptic meningitis
  • Encephalitis
  • Orchitis after puberty, usually unilateral
  • Pancreatitis
  • Oophoritis
  • Thyroiditis
98
Q

Mumps

Diagnosis

A
  • Clinical diagnosis
    • Symptoms
    • Current medical conditions
    • Current medications
    • Family hx of medical conditions
  • Physical exam helps
  • Serology for Ab
  • Throat culture for virus
  • Lumbar puncture to ID virus in CSF
99
Q

Mumps

Treatment

A
  • No effective antivirals for established infection
  • Supportive treatment
    • Antipyretics and analgesics
    • Vit A recommended for children w/ measles but does not help with mump
100
Q

Mumps

Prevention

A
  • MMR ⇒ live, attenuated mumps vaccine
    • Greatly ↓ incidence
    • Children ≥ 1 y/o get 2 doses
      • Between 15-18 m/o
      • Between 4-6 y/o

2. HDS Pulmonary (28 decks)

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