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Miguel > Respiratory syncytial virus > Flashcards

Respiratory syncytial virus Flashcards

1
Q

In what year was RSV first isolated?

A

1957

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2
Q

In what year was the first FI-RSV vaccine discovered?

A

1967
2 kids died in orphanage in Washington, turns out it enhanced the disease.

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3
Q

Who are increasingly concerned by RSV infection?

A

Elderly

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4
Q

WHO published that there are greater than _____________ new infections of RSV every year.

A

60 million

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5
Q

________ are affected the most by RSV.

A

Infants

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6
Q

RSV induces (2) in 25-40% of patients during first infection

A

Severe bronchitis
Pneumonia

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7
Q

RSV-induced diseases in order of descending infection

A

Rhinitis
Otitis media
Tracheobronchitis
Bronchiolitis
Pneumonia
Asthma

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8
Q

Bronchiolitis features

A

Small airway epithelium necrosis and sloughing
Oedema
Increased mucus secretion

Hyperinflation due to trapped air below mucus plugs
Atelectasis - collapsed lung
Wheezing

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9
Q

Pneumonia features

A

Interstitial infiltration
Alveolar filling
Consolidation

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10
Q

In _______ the airway becomes obstructed from swelling of the _______ ____.

A

Bronchiolitis
Bronchiole walls

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11
Q

What are the principle infiltrates in RSV Bronchiolitis?

A

PMN
Lymphocytes
Eosinophils (Low)

(Immune mediated disease)

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12
Q

RSV epidemiology

A

Ubiquitous pathogen
Two subgroups A and B
Seasonal epidemics
- late autumn to early spring in temperate climates
- rainy season in tropical climates

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13
Q

The greatest number of reports of RSV was in the year ________

A

1999- 2000

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14
Q

Which age is most affected by RSV? (Number)

A

<1

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15
Q

How is RSV transmitted?

A

Close personal contact
- sneeze
- handshake
- contaminated surfaces
- nosocomial

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16
Q

Define nosocomial

A

Nosocomial infections also referred to as healthcare-associated infections (HAI), are infection(s) acquired during the process of receiving health care that was not present during the time of admission

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17
Q

What is the incubation time for RSV?

A

2-8 days

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18
Q

What is the infection time of RSV in (a) adults and (b) infants?

A

3 days
3 weeks

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19
Q

How many RSV deaths per year?

A

160,000

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20
Q

3 groups at risk of severe RSV disease

A

Infants
Frail elderly
Immunocompromised - especially bone marrow transplant recipients

bone marrow transplant -> eliminates immune system -> donor marrow replaces -> takes a period of time for immune response to kick in

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21
Q

What is the mortality rate of immunocomprosimsed individuals with RSV?

A

30-100%

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22
Q

Risk factors for severe RSV disease in infants (9)

A

Prematurity (born more than 4 weeks early)
Chronic lung disease or congenital heart disease
Low birth weight
Child care or day care attendance
School-age brothers and sisters at home
Crowded living conditions
Multiple births
Family history of asthma
Exposure to tobacco smoke or other environmental air pollutants

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23
Q

In the USA from 1993 to 1999 RSV infections have __________.

24
Q

What age group made up 38% of RSV hospitalisations in USA?

A

0-2 months

25
What age group has the greatest incidence of RSV in Denmark?
1 month
26
______ is the most common cause of LRI of infants < 6 months old worldwide.
RSV
27
Features of RSV in the 15-44yo age group
11-24% GP visits for acute Resp illness
28
Features of RSV in the ≥45yo age group
23-40% GP visits for acute respiratory illness
29
Features of RSV in the >65yo age group
Frequent cause of flu-like symptoms, Bronchiolitis and pneumonia 14-60,000 hospitalisations per year (USA) 1480 - 6660 deaths per year (USA)
30
Pathology off Bronchiolitis and pneumonia in RSV
Necrosis and sloughing of small airway epithelium Oedema Increased mucus secretion - obstructs airflow in small airways Interstitial infiltration Alveolar filling
31
Clinical presentations in Bronchiolitis and pneumonia in RSV
Hyperinflation Atelectasis Wheezing
32
Atelectasis
Collapsed lung
33
Interventions for Bronchiolitis
Oxygen Cardiorespiratory monitor and pulse oximeter Aerolized bronchodilator - Albuterol - Racemic epinephrine Assure hydration - IV
34
RSV prevention and treatment
N͟o vaccines N͟o therapeutics Monoclonal antibodies Phase 3 clinical trials for maternal and elderly vaccine
35
Two monoclonal antibodies used to treat RSV
Palivizumab Nirsevimab
36
Palivizumab (Synagis) RSV prophylaxis
1st anti-RSV MAb on market High risk infants Helps prevent serious LR tract illness Anti-F protein humanised monoclonal antibody High neutralising activity Monthly injections throughout RSV season
37
What was the 1st monoclonal licensed against any infectious disease?
Palivizumab
38
What’s the difference between Nirsevimab and Palivizumab?
Nirsevimab is a single injection to last the whole RSV season; longer immunity due to a mutated Fc domain; due to the need for only one dose, Nirsevimab is a cheaper treatment option
39
Two types of mononegavirales
Penumonviridae Paramyxoviridae
40
Subtypes of penumonvirdae and an example
Orthopneumovirus - RSV Metapneumovirus - Human metapneumovirus
41
Paramyxoviridae subtypes and examples
Respirovirus - Sendai virus Rubulovirus - mumps virus Morbillivirus - measles virus
42
Virus-infected epithelium causes (6)
Plasma leakage Inflammatory cell recruitment and activation Cytokine and chemokine release Neural activation Airway hyperesponsiveness - cough Mucus hypersecretion
43
WD-PBEC model
Well-differentiated primary bronchial epithelial cell model Bronchial brushings from healthy children during elective surgery Cells plated into plastic ware in lab (medium in apical and basal compartment) Exposure to air when confluent 3D WD-PBECs staining
44
Characterisation of the WD-PBEC model
B-Tubulin -> ciliated cells👋 MUC5AC -> mucus producing cells ZO-1 -> tight junctions
45
WD-PBECS model is representative of _____________________.
Lung physiology
46
RSV infects _______ cells.
Ciliated
47
RSV induces ___________ formation
Syncytia
48
RSV induces apical _____ ___________.
Cell sloughing
49
Cells involved in the immune response to RSV
Cellular infection triggers the release of early **inflammatory mediators**, e.g., TNF and IFN-α/β. **NK** cells and **PMN** are recruited in the first **3 days** of infection, at which time **DC** carry viral antigen to local lymph nodes and **present** it to **CD4+ T cells**. Once **primed**, these cells **migrate** back to the **infected epithelium**, **release further mediators**, and **recruit** additional inflammatory cells, including mononuclear cells (**including CD8+ T cells and B cells**) and granulocytes (e.g., **neutrophils [PMN] and eosinophils [Eo]**).
50
Explain the altering of RSV F configuration upon fusion
Pre F: metastable Several antibody epitopes Vaccine candidate Post F: highly stable Some antibody epiptopes lost
51
RSV re-infection
Common throughout life - incomplete acquired immunity LRI frequency and severity reduced upon re-infection - accumulating protective immunity
52
High maternal neutralising antibody titres correlate with
Reduced LRI severity
53
RSV stands for
Respiratory Syncytial Virus
54
RSV Structure
Surface glycoprotein - G, Fusion, M2 Envelope - derived from cell membrane Matrix protein - gives shape Helical nucleocapsid SS RNA genome RNA dependent RNA polymerase complex composed of P & L protein
55
What is an FI-vaccine?
Formalin inactivated vaccine
56
Vaccines against RSV and influenza aim to
Induce F protein to maintain pre-fusion structure so they can be cleared by the host immune system before the conformational change.

Miguel (8 decks)

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