respiratory tract infections Flashcards

1
Q

what is the epidemiology of respiratory tract infections?

A

adults get 4-6 colds a year
only a tiny proportion of these result in more severe disease

overall less than a 0.005% infection-fatality rate

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2
Q

what are the different types of respiratory tract infections?

A
upper RTI:
A cough
Sneezing
A runny or stuffy nose
A sore throat
headache
least severity 
lower RTI:
A “productive” cough - phlegm
Muscle aches
Wheezing
Breathlessness
Fever
Fatigue
pneumonia:
Chest pain 
Blue tinting of the lips
Severe fatigue
High Fever
most severe

1 -> 2 -> 3

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3
Q

what is the health burden of RTIs?

A

Respiratory infection resulted in an estimated 5 million deaths annually between 1990 and 2015. About 3 million deaths annually from acute lower respiratory infection.

worse in developing countries, especially sub saharan africa

lower RTIs are one of the leading causes of death in the world (4th) (not including TB)

ranked highest in terms of DALYS (Disability-adjusted Life Year
A sum of Years of Life Lost (YLL) and Years Lost to Disability (YLP))

way worse in people over 70
higher rates of pneumonia above 70
higher mortality

also higher mortality in children under 5
leading cause of mortality up to one year

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4
Q

what are the risk factors for pneumonia?

A

Demographic and lifestyle factors:
Age <2 years or >65 years
Cigarette smoking
Excess alcohol consumption

Social factors:
Contact with children aged <15 years
Poverty
Overcrowding

Medications:
Inhaled corticosteroids
Immunosuppressants (e.g steroids)
Proton pump inhibitors

Medical history:
COPD, Asthma
Heart disease
Liver disease
Diabetes mellitus
HIV, Malignancy, Hyposplenism
Complement or Ig deficiencies
Risk factors for aspiration
Previous pneumonia
Specific risk factors for certain
pathogens
Geographical variations
Animal contact
Healthcare contacts
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5
Q

what are the causative agents of respiratory infections?

A

bacterial

viral

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6
Q

what are the main bacteria that cause RTIs?

A

Streptococcus pneumoniae

Mycoplasma pneumoniae

Haemophilus Influenzae

Mycobacterium tuberculosis

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7
Q

what are the main viruses that cause RTIs?

A
Influenza A or B virus
Respiratory Syncytial Virus
Human metapneumovirus
Human rhinovirus
Coronaviruses
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8
Q

what are some facts about COVID-19

A

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)
Causative agent of coronavirus disease first observed in 2019 (COVID-19)

Asymptomatic respiratory pneumonia and lung failure.

Up to November 2021
250 million cases
5 million deaths.

same risk factors as other RTIs

leading cause of death in 2020 in the UK

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9
Q

what is community acquired pneumonia (causes)?

A

CAP

Bacterial:
Streptococcus pneumoniae (40-50%)
Mycoplasma pneumoniae
Staphylococcus aureus
Chlamydia pneumoniae
Haemophilus Influenzae

Streptococcus pneumoniae
Gram-positive, extracellular, opportunistic pathogen.
as it is gram positive it can be treated with penicillin

tend to be more typical

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10
Q

what is hospital acquired pneumonia (causes)?

A
bacterial:
Staphylococcus aureus
Psuedomonas aeruginosa
Klebsiella species
E. Coli
Acinetobacter spp.
Enterobacter spp.

Ventilator associated pneumonia:
Psuedomonas aeruginosa (25%)
Staphylococcus aureus(20%)
Enterobacter

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11
Q

what are typical vs atypical pneumonias?

A

Atypical pneumonias present with slightly different symptoms (some with longer milder symptoms for instance).

Atypical pneumonias are often more difficult to culture (hence atypical) and may require a different antibiotic regime to treat them.

Penicillins often given for typical pneumonia, additional macrolides may be administered for atypical.

Examples of typical - Common:
Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis

Examples of atypical:
Mycoplasma pneumoniae, Chlamydia pneumoniae,
Legionella pneumophilia

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12
Q

what are the mechanisms of damage in acute bacterial pneumonia?

A

inflammatory

Pneumonia:
Inflammation and swelling of the alveoli

(whereas:
Bronchitis- 
inflammation and swelling of the bronchi
Bronchiolitis- 
Inflammation and swelling of the bronchioles)

lung injury -> arterial hypoxaemia -> ARDS

bacteraemia -> organ infection -> sepsis

systemic inflammation -> organ infection -> sepsis

and all of the above lead to deterioration

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13
Q

how is bacterial pneumonia graded?

A

CRB-65
CURB-65 if in hospital

C - confusion
R - respiratory rate >30 breaths per min
B - blood pressure <90 systolic and/or 60 diastolic
65 - age 65 years or older

U - urea >7 mmol/L

presence of each category scores one point
treatment according to overall points

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14
Q

how is bacterial pneumonia treated?

A
Supportive Therapy:
Oxygen (for hypoxia)
Fluids (for dehydration)
Analgesia (for pain)
Nebulised saline (may help expectoration)
Chest physiotherapy?

Antibiotics:
Penicillins e.g. amoxicillin – beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation
Macrolides e.g. clarithromycin – bind to the bacterial ribosome to prevent protein synthesis

treatment differs depending on CRB-65 staging

Add a macrolide to penicillin for atypical

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15
Q

can you catch pneummonia?

A

not really
the bacteria mostly live on the body, so you catch it from yourself

Oropharynx:
Strep. viridans
Coagulase neg. staph
Veronella
Fusiforms
Treponena spp.
Beta-haem. strep
*Haemophilus spp.*
*Staph. aureus*
*Strep. pneumoniae*
Nose:
Coagulase neg. staph
Haemophilus spp.
Staph. aureus
Strep. viridans
*Strep. pneumoniae*dd
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16
Q

why do viral infections result in disease?

A

viral infection leads to:
mediator release
cellular inflammation
local immune memory

it also leads to damage to the epithelium which leads to:
loss of cilia
bacterial growth 
poor barrier to antigen
loss of chemoreceptors
17
Q

what causes severe disease?

A
  1. Highly pathogenic strains (zoonotic)
  2. Absence of prior immunity -
    Innate immunodeficiency
    B cells
    T cells
  3. Predisposing illness/conditions -
    Frail elderly
    COPD/asthma
    Diabetes, obesity, pregnancy etc.
18
Q

what is virus tropism?

A

where it infects

eg.
2009 - H1N1 influenza A
Haemogglutinin binds 𝛂2,6 sialic acids
more nasal epithelium, so more upper RTI, so less severe

2012 - H5N1 avian Flu
Haemogglutinin binds 𝛂2,3 sialic acids
more lower, so more severe

19
Q

how do epithelial cells act as the first line of defence?

A

Respiratory epithelium:
Tight junctions – prevents systemic infection

Mucous lining and cilial clearance – prevents attachment, clears particulates

Antimicrobials – recognise, neutralize and/or degrade microbes and their products

Pathogen recognition receptors – recognise pathogens either outside or inside a cell.

Interferon pathways – activated by viral infection. Promotes upregulation of anti-viral proteins and apoptosis.

20
Q

what is a serotype?

A

viruses which cannot be recognized by serum (really antibodies) that recognize another virus – implications for protective immunity

eg. why it is so hard to make a flu vaccine

21
Q

what do serotypes tell us about viral immunity?

A

(Antibody mediated immunity
Humoral immunity:
Adaptive, so dependent on prior exposure
B cells activated to differentiate into antibody secreting plasma cells
Different antibody classes provide different biochemical properties and functions)

nasal cavity:
Enriched for IgA
High frequency of IgA-plasma cells
ECs express poly IgA receptor, allowing export of IgA to the mucosal surface
Homodimer is extremely stable in protease rich environment

lung epithelium:
Enriched for IgGs
Thin-walled alveolar space allows transfer of plasma IgGs into the alveolar space

22
Q

what is RSV broncholitis like in children?

A

Leading cause of infant hospitalization in the developed world

50% of children infected in year 1 of life, all children by year 3.

1% develop severe bronchiolitis.

Can repeatedly infect children.

Risk factors
Premature birth
Congenital heart and lung disease

symptoms:
nasal flaring
hypoxia and cyanosis
croupy cough
expiratory wheezing
prolonged expiration
fast breathing with apneic episodes
23
Q

what are possible treatments for viral RTIs?

A
Supportive Therapy:
Oxygen (for hypoxia)
Fluids (for dehydration)
Analgesia (for pain)
Nebulised saline (may help expectoration)
Chest physiotherapy?
Preventative/prophylactic:
Vaccines:
Major surface antigen – spike protein
Viral vector (e.g. adenovirus vaccine e.g. Oxford/AZ)
mRNA vaccines (e.g. 

Therapeutic:
Anti inflammatory
Dexamethasone (steroids)
Tocilizumab (Anti-IL6R) or Sarilumab (anti-IL6)

preventative and theraputic:
Anti-virals
Remdesivir – broad spectrum antiviral – blocks RNA-dependent RNA polymerase activity
Paxlovid – antiviral protease inhibitor
Casirivimab and imdevimab - monoclonal neutralising antibodies for SARS-CoV-2

24
Q

what is the interplay between viral and bacterial infections?

A

viral may damage the epithelium, leading to increased susceptibility to bacterial infections

maybe not all deaths from spanish flu were actually caused by the viral influenza?

25
Q

what is the interplay between viral RTIs and lung disease?

A

Viral bronchiolitis is associated with the development of asthma

Rhinoviruses are the most common cause of asthma and COPD exacerbations

High likelihood of secondary bacterial pneumonia after viral infection