Viral Respiratory Pathogens Flashcards

(100 cards)

1
Q

Respiratory Viruses

Categories

A
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2
Q

Viral Respiratory Infections

Overview

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  • 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

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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
Coronavirus Transmission
* Aerosols of respiratory secretions * Direct transmission via fomites * Fecal-oral transmission rare
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Coronavirus Epidemiology
* **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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Coronavirus Symptoms
* **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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Coronavirus Dx, Tx, and Prevention
* 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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SARS Overview
**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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SARS Symptoms
* 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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SARS Diagnosis
* PCR of two sites or two different times * ELISA test for Ab
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MERS Overview
**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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MERS Clinical Presentation
* **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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MERS Symptoms
* Fever \> 38°C or 100.4°F * Cough * SOB * Malaise * Vomiting * Diarrhea * PNA
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MERS Transmission and Epidemiology
* **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**
36
COVID-19 Overview
**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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COVID-19 Transmission
* **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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COVID-19 Clinical Presentation
* 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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COVID-19 Testing
* PCR from anterior nasal swab * ELISA test for Ab
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Novel Coronaviruses Comparison
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Adenovirus Characteristics
* 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
Adenovirus Capsid Structure
* **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
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Adenovirus Clinical Features
* **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
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Advenovirus Transmission
* 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**
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Advenovirus Pathogenesis
* 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
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Adenovirus Clinical Syndromes
* 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
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Swimming Pool Adenovirus
**"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
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Adenovirus Diagnosis
* **Immunoassays** * Fluorescent Ab * Enzyme-linked immunosorbent assays * **PCR** * Detect & type virus in clinical samples * **Serological assays** * CFA, HI, EIA * Neutralization techniques * Rarely used
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Adenovirus Treatment and Prevention
* 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
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Parainfluenza virus Characteristics
* 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
Parainfluenza Structure
* **Linear nucleocapsid** * Envelop contains * **Hemagglutinin/neuraminidase** * **Fusion F protein**
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Parainfluenza Clinical Features
* **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
Parainfluenza Transmission
* **Direct person-to-person contact** * **Large droplet aerosols** * Infectious for \> 1 hour
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Parainfluenza Clinical Syndromes
* **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
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Parainfluenza Pathogenesis
* Viruses multiply throughout tracheobronchial tree * Induces production of mucus * **Vocal cords of larynx become grossly swollen** * Obstructs inflow of air ⇒ **inspiratory stridor**
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Parainfluenza Genetics
**Parainfluenza more genetically stable than influenza virus:** Very little mutation Minimal antigenic drift No antigenic shift
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Parainfluenza Immunity
* **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
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Parainfluenza Dx, Tx, Prevention
* 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**
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Influenza Characteristics
* Family ⇒ Orthomyxoviridae * **Enveloped virus** * Spikes extend from envelope ⇒ major Ag * **Segmented ⊖-sense ssRNA** * 3 types ⇒ Influenza A, B, C
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Influenza Envelop Structure
**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
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Influenza Genome
**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
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Influenza Genetic Changes
* Flu A ⇒ antigenic shift and drift * Flu B ⇒ antigenic drift only * Flu C ⇒ relatively stable
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Influenza Classification
* **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
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Influenza Nomenclature
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)
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Influenza Clinical Features
* 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**
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Influenza Transmission
* **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**
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Influenza Symptoms
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
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Influenza Complications
* PNA ⇒ viral and bacterial * Croup * Asthma * Bronchitis * Myocarditis and pericarditis * Death
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Influenza Pathogenesis
* _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**
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Influenza Immunity
* **IFN-𝛾** ⇒ limits spread of disease * **Cytotoxic T-cells** ⇒ limit shed of virus by killing infected cells * **Ab** ⇒ induced and limits subsequent infections
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Influenza Epidemiology
* **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
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Influenza Diagnosis
* **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
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Influenza Treatment
* **_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
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Influenza Prevention
* **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
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"Flu Shot"
* **Inactivated killed virus vaccine** * Whole virus * Subvirion * Surface Ag preparations * Given IM \> intradermal * Approved for \> 6 m/o * Healthy or w/ chronic medical conditions
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Live Attenuated Influenza Vaccine | (LAIV)
* **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
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Influenza Pandemics
**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
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Antigenic Drift
* **Point mutations accumulate** ⇒ ∆ AA in protein * **Immune system selects for advantagous ∆** * Does not cause variation * **Need ≥ 2 mutations** before new epidemiologically significant strain emerges
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Antigenic Shift
* **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**
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Respiratory Syncytial Virus (RSV) Characteristics
* 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
RSV Virulence Factors
**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
RSV Clinical Features
* **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
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RSV Transmission
* **Aerosol** ⇒ sneezing * **Direct transmisson** ⇒ fomites, contagious secretions * **Highly infectious and ubiquitious** * ~100% of children infected by 2 y/o
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RSV Symptoms
_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
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RSV At-Risk Infants
* **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
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RSV Pathogenesis
* **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_
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RSV Diagnosis
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
RSV Treatment
1. **Symptomatic** 2. **Aerosolized ribavarin** * Used for infants w/ severe infection * Used for those at risk of severe disease * ? Utility
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RSV Prevention
* **Passive immunization** ⇒ Palivizumab (Synagis) * Expensive * **Live attenuated vaccine** * Under development * Deaths associated w/ inactivated vaccine in 1960's
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RSV Immunoprophylaxis
_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
Mumps Virus Characteristics
"Mumps" * **Paramyxovirus genus** * **Rubulavirus family** * Pleomorphic, **enveloped** virus w/ **helical nucleocapsid** * **⊖-sense ss-RNA** * Only one mumps serotype * Humans are the only natural host
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Mumps Virus Envelope Structure
_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
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Mumps Clinical Features
* 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
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Mumps Virus Transmission
_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
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Mumps Symptoms
* Sore throat * Fever * Tiredness * Muscle and body aches * Loss of appetite * Chills * Pain w/ chewing or swallowing * Salivary gland swelling
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Mumps Pathogenesis
* **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
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Mumps Complications
* Aseptic meningitis * Encephalitis * Orchitis after puberty, usually unilateral * Pancreatitis * Oophoritis * Thyroiditis
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Mumps Diagnosis
* **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
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Mumps Treatment
* **No effective antivirals for established infection** * **Supportive treatment** * Antipyretics and analgesics * Vit A recommended for children w/ measles but does not help with mump
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Mumps Prevention
* **MMR ⇒ live, attenuated mumps vaccine** * Greatly ↓ incidence * Children ≥ 1 y/o get 2 doses * Between 15-18 m/o * Between 4-6 y/o