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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 __________.

A

RiZZen

24
Q

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

A

0-2 months

25
Q

What age group has the greatest incidence of RSV in Denmark?

A

1 month

26
Q

______ is the most common cause of LRI of infants < 6 months old worldwide.

A

RSV

27
Q

Features of RSV in the 15-44yo age group

A

11-24% GP visits for acute Resp illness

28
Q

Features of RSV in the ≥45yo age group

A

23-40% GP visits for acute respiratory illness

29
Q

Features of RSV in the >65yo age group

A

Frequent cause of flu-like symptoms, Bronchiolitis and pneumonia
14-60,000 hospitalisations per year (USA)
1480 - 6660 deaths per year (USA)

30
Q

Pathology off Bronchiolitis and pneumonia in RSV

A

Necrosis and sloughing of small airway epithelium
Oedema
Increased mucus secretion
- obstructs airflow in small airways
Interstitial infiltration
Alveolar filling

31
Q

Clinical presentations in Bronchiolitis and pneumonia in RSV

A

Hyperinflation
Atelectasis
Wheezing

32
Q

Atelectasis

A

Collapsed lung

33
Q

Interventions for Bronchiolitis

A

Oxygen
Cardiorespiratory monitor and pulse oximeter
Aerolized bronchodilator
- Albuterol
- Racemic epinephrine
Assure hydration - IV

34
Q

RSV prevention and treatment

A

N͟o vaccines
N͟o therapeutics
Monoclonal antibodies
Phase 3 clinical trials for maternal and elderly vaccine

35
Q

Two monoclonal antibodies used to treat RSV

A

Palivizumab
Nirsevimab

36
Q

Palivizumab (Synagis) RSV prophylaxis

A

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
Q

What was the 1st monoclonal licensed against any infectious disease?

A

Palivizumab

38
Q

What’s the difference between Nirsevimab and Palivizumab?

A

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
Q

Two types of mononegavirales

A

Penumonviridae
Paramyxoviridae

40
Q

Subtypes of penumonvirdae and an example

A

Orthopneumovirus
- RSV

Metapneumovirus
- Human metapneumovirus

41
Q

Paramyxoviridae subtypes and examples

A

Respirovirus
- Sendai virus

Rubulovirus
- mumps virus

Morbillivirus
- measles virus

42
Q

Virus-infected epithelium causes (6)

A

Plasma leakage
Inflammatory cell recruitment and activation
Cytokine and chemokine release
Neural activation
Airway hyperesponsiveness - cough
Mucus hypersecretion

43
Q

WD-PBEC model

A

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
Q

Characterisation of the WD-PBEC model

A

B-Tubulin -> ciliated cells👋
MUC5AC -> mucus producing cells
ZO-1 -> tight junctions

45
Q

WD-PBECS model is representative of _____________________.

A

Lung physiology

46
Q

RSV infects _______ cells.

A

Ciliated

47
Q

RSV induces ___________ formation

A

Syncytia

48
Q

RSV induces apical _____ ___________.

A

Cell sloughing

49
Q

Cells involved in the immune response to RSV

A

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
Q

Explain the altering of RSV F configuration upon fusion

A

Pre F: metastable
Several antibody epitopes
Vaccine candidate

Post F: highly stable
Some antibody epiptopes lost

51
Q

RSV re-infection

A

Common throughout life
- incomplete acquired immunity
LRI frequency and severity reduced upon re-infection
- accumulating protective immunity

52
Q

High maternal neutralising antibody titres correlate with

A

Reduced LRI severity

53
Q

RSV stands for

A

Respiratory Syncytial Virus

54
Q

RSV Structure

A

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
Q

What is an FI-vaccine?

A

Formalin inactivated vaccine

56
Q

Vaccines against RSV and influenza aim to

A

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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