Respiratory Tract Infections & Immunity Flashcards
Outline the epidemiology of respiratory infections (Deaths / Age 3).
Deaths:
* Estimated 5 million deaths annually between 1990 - 2015
* About 3 million deaths annually from acute lower respiratory infections
Age:
* Age dramatically impacts mortality burden
* Over 70
* Under 5
* Pneumonia rates increase with age
Mortality burden definition:
* DALY – Disability-adjusted Life Year: A sum of Years of Life Lost (YLL) and Years Lost to Disability (YLP)
What are the risk factors of respiratory infections (pneumonia) divided into (5)?
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
* Immunosuppresants (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
What are the demographic and lifestyle risk factors of respiratory infections (pneumonia) (3)?
Demographic and lifestyle factors:
* Age < 2 years or > 65 years
* Cigarette smoking
* Excess alcohol consumption
What are the social risk factors of respiratory infections (pneumonia) (3)?
Social factors:
* Contact with children aged < 15 years
* Poverty
* Overcrowding
What are the medication risk factors of respiratory infections (pneumonia) (3)?
Medications:
* Inhaled corticosteroids
* Immunosuppresants (e.g steroids)
* Proton pump inhibitors (PPIs)
What are the medical history risk factors of respiratory infections (pneumonia) (11 / know 5)?
Medical history:
* COPD
* Asthma
* Heart disease
* Liver disease
* Diabetes mellitus
* HIV
* Malignancy
* Hyposplenism
* Complement or Ig deficiencies
* Risk factors for aspiration
* Previous pneumonia
What are the specific risk factors for certain pathogens of respiratory infections (pneumonia) (3)?
Specific risk factors for certain pathogens:
* Geographical variations
* Animal contact
* Healthcare contacts
Outline the pathogenesis of respiratory infections (2).
Through (common) causative agents:
Bacterial:
* Streptococcus pneumoniae
* Myxoplasma pneumoniae
* Haemophilus Influenzae
* Mycobacterium tuberculosis
Viral:
* Influenza A or B virus
* Respiratory Syncytial Virus
* Human metapneumovirus
* Human rhinovirus
* Coronaviruses
What are the common bacterial causes of respiratory infections (4)?
Bacterial:
* Streptococcus pneumoniae
* Myxoplasma pneumoniae
* Haemophilus Influenzae
* Mycobacterium tuberculosis
What are the common vacterial causes of respiratory infections (5)?
Viral:
* Influenza A or B virus
* Respiratory Syncytial Virus
* Human metapneumovirus
* Human rhinovirus
* Coronaviruses
How would a patient with upper respiratory tract infection present (5)?
- Cough
- Sneezing
- Runny or stuffy nose
- Sore throat
- Headache
How would a patient with lower respiratory tract infection present (6)?
- A “productive” cough - phlegm
- Muscle aches
- Wheezing
- Breathlessness
- Fever
- Fatigue
How would a patient with pneumonia present (4)?
Pneumonia is a medical condition that affects the lungs, characterized by inflammation of the air sacs in one or both lungs, which can be caused by a variety of infectious agents such as bacteria, viruses, or fungi.
- Chest pain
- Blue tinting of the lips
- Severe fatigue
- High fever
What are the 3 different types of pneumonia?
- Community acquired pneumonia (CAP)
-
Hospital acquired pneumonia (HAP)
- Ventilator associated pneumonia (VAP)
What are the main bacterial causes of community acquired pneumonia (CAP) (5)?
- Streptococcus pneumoniae (40-50%)
- Myxoplasma pneumoniae
- Staphylococcus aureus
- Chlamydia pneumoniae
- Haemophilus Influenzae
What are the main bacterial causes of hospital acquired pneumonia (HAP) (6)?
- Staphylococcus aureus
- Psuedomonas aeruginosa
- Klebsiella species
- Escherichia coli (E. coli)
- Acinetobacter spp.
- Enterobacter spp.
What are the main bacterial causes of ventilator acquired pneumonia (VAP) (3)?
- Psuedomonas aeruginosa (25%)
- Staphylococcus aureus (20%)
- Enterobacter
What are the most typical causes of pneumonia (3)?
- Streptococcus pneumoniae
- Haemophilus influenzae
- Moraxella catarrhalis
What are the most atypical causes of pneumonia (3)?
- Mycoplasma pneumoniae
- Chlamydia pneumoniae
- Legionella pneumophilia
Outline the pathophysiology of acute bacterial pneuonia.
What is CURB-65 scoring?
- A grading potential bacterial pneumonia
Describe the CURB-65 scoring system.
- Confusion
- (In hospital add) Urea
- > 7 mmol/L
-
Respiratory rate
- > 30 breaths/min
-
Blood pressure
- < 90 systolic and / or 60 mmHg diastolic
- 65 years old or older
1 point per item
What is the management of bacterial pneumonia divided into (2)?
- Supportive therapy
- Treatments
What is the supportive therapy recommended for the management of bacterial pneumonia (5)?
- Oxygen (for hypoxia)
- Fluids (for dehydration)
- Analgesia (for pain)
- Nebulised saline (may help expectoration)
- Chest physiotherapy
What is the treatment for the management of bacterial community accquired pneumonia (CAP) with CURB-65 score of 0 (1)?
Penicillins
* Amoxicillin (or clarithromycin/ doxycycline if pen. allergic)
Penicillins e.g. amoxicillin – beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation
What is the treatment for the management of bacterial hospital accquired pneumonia (HAP) with CURB-65 score of 0 (1)?
Penicillins
* NOT SEVERE: doxycycline PO
Penicillins e.g. amoxicillin – beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation
What is the treatment for the management of bacterial community accquired pneumonia (CAP) with CURB-65 score of 1-2 (2)?
Penicillins + Macrolides
* Amoxicillin + clarithromycin (or clarithro./doxy.)
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
What is the treatment for the management of bacterial community accquired pneumonia (CAP) with CURB-65 score of 3-4 (2)?
Penicillins + Macrolides
* Benzyl-penicillin IV + clarithro. PO (or teicoplanin + clarithro.)
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
What is the treatment for the management of bacterial hospital accquired pneumonia (HAP) with CURB-65 score of 3-4 (2)?
Penicillins + Macrolides
* SEVERE: tazocin (piperacillin-tazobactam) IV +/- gentamicin IV
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
Outline the pathogenesis of viral respiratory infection.
- Highly pathogenic strains (zoonotic)
-
Absence of prior immunity
Innate immunodeficiency (e.g. IFITM3 gene variant)
B cells (antibody- presumably local)
T cells (correlate with peripheral levels?) -
Predisposing illness/conditions
Frail elderly
COPD/asthma
Diabetes, obesity, pregnancy etc.
How is the respiratory epithelium designed to resist infections (5)?
- Tight junctions: prevents systemic infection
- Mucous lining and cilial clearance: prevents attachment, clears particulates
- Antimicrobials: recognise, neutralise 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.
What is antibody mediated immunity (humoral immunity) (2)?
- 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
How is the nasal cavity and bronchi designed to resist infections (2)?
Outline the pathophysiology of viral respiratory infections.
What is the supportive therapy recommended for the management of viral respiratory infections (5)?
- Oxygen (for hypoxia)
- Fluids (for dehydration)
- Analgesia (for pain)
- Nebulised saline (may help expectoration)
- Chest physiotherapy
What is the preventative / prophylactic therapy recommended for the management of viral respiratory infections (1)?
-
Vaccines
- Major surface antigen – spike protein
- Viral vector (e.g. adenovirus vaccine e.g. Oxford/AZ)
- mRNA vaccines (e.g. BioNtech/Pfizer)
What is the treatment recommended for the management of viral respiratory infections (2)?
Anti-inflammatory
* Dexamethasone (steroids)
* Tocilizumab (anti-IL-6R) or Sarilumab (anti-IL-6)
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
What anti-inflammatory medication is recommended for the management of viral respiratory infections (3)?
- Dexamethasone (steroids)
- Tocilizumab (anti-IL-6R)
- Sarilumab (anti-IL-6)
What anti-viral medication is recommended for the management of viral respiratory infections (3)?
- Remdesivir – broad spectrum antiviral – blocks RNA-dependent RNA polymerase activity
- Paxlovid – antiviral protease inhibitor
- Casirivimab and imdevimab - monoclonal neutralising antibodies for SARS-CoV-2