Respiratory Tract Infection and Immunity Flashcards
What are the symptoms of upper respiratory tract infection?
- cough
- sneezing
- runny or stuffy nose
- sore throat
- headache
What are the symptoms of lower respiratory tract infection?
- a productive cough : phlegm
- muscle aches
- wheezing
- breathlessness
- fever
- fatigue
What are the symptoms of pneumonia?
- chest pain
- blue tinting of lips
- severe fatigue
- high fever
What is Disability-adjusted Life Year?
sum of Years of Life Lost (YLL) and Years Lost to Disability (YLP)
What is the impact of age on mortality?
dramatically increases mortality once age is greater than 70 years
What is the leading cause of death in those younger of 5?
malaria, then lower respiratory infections (pneumonia and bronchitis)
What are the different forms of pneumonia?
- community acquired pneumonia
- hospital acquired pneumonia
- ventilator associated pneumonia
What are the main causes of community acquired pneumonia?
- streptococcus pneumoniae (40-50%)
- myxoplasma pneumoniae
- staphlococcus aureus
- chlamydia pneumoniae
- haemophilus influenzae
What are the main causes of hospital acquired pneumonia?
- Staphylococcus aureus
- Pseudomonas aeruginosa
- Klebsiella species
- E. Coli
- Acinetobacter spp.
- Enterobacter spp.
What are the main causes of ventilator associated pneumonia?
- pseudomonas aeruginosa (20%)
- staphylococcus aureus (20%)
- enterobacter
What strains present as ‘walking’ (atypical) pneumonias?
- mycoplasma pneumoniae
- chlamydia pneumoniae
- legionella pneumophilia
What are the mechanisms of damage of pneumonia?
- bronchitis (bronchi inflammation)
- bronchiolitis (bronchiole inflammation)
- pneumonia (alveoli inflammation)
How do you grade potential bacterial pneumonia?
- using the CRB/CURB-65 scoring system
What does CRB/CURB-65 mean?
- Confusion
- Respiratory rate (>30 breaths/min)
- Blood pressure (<90 systolic and/or 60mmHg diastolic)
- 65 (>65 years or older)
In hospital, add: - Urea (7mmol/L)
What is the difference between CRB and CURB-65?
CURB-65 is used in hospital, add Urea (7mmol/L)
What are the different classifications for CRB and CURB-65?
0 - low severity (home treatment, anitbiotics)
1-2 - moderate severity (hospital referral)
3-4 - high severity (urgent admission, empirical antibiotics)
What are the treatments for bacterial pneumonia?
- supportive therapies
- antibiotics
What are the different supportive therapies are used to treat pneumonia?
- oxygen (for hypoxia)
- fluids (for dehydration)
- analgesia (for pain)
- nebulised saline (for expectoration)
- chest physiotherapy
What is the impact of the time of administration on survival rate?
the earlier the better (<8hours) after admission
Is bacterial pneumonia infectious/contagious?
- Not commonly contagious
- Most of the bacteria is present in the microbiome of oropharynx, nose, oral cavity, they’re commensal bacteria
What is an opportunistic pathogen?
a microbe that takes advantage of a change in conditions (often immunosuppression)
What is a pathobiont?
a microbe that is normally commensal, but found in the wrong environment can cause pathology
What does cloudiness on the x-ray indicate?
fluid in the lungs
Why do viral infections result in disease?
causes:
- cellular inflammation (mediator release)
- damage to epithelium (cilia loss, poor barrier, chemoreceptor loss, bacterial growth)
What are the factors that cause severe disease?
- highly pathogenic strains
- absence of prior immunity
- predisposing illness/conditions
What does zoonotic mean?
highly pathogenic strains
What is viral tropism?
the ability of a virus to infect a particular cell
What are the features of the respiratory epithelium?
- tight junctions (prevents systemic infection)
- mucous lining and cilial clearance (prevents attachment)
- antimicrobials (recognise and neutralise)
- pathogen recognition receptors
- interferon pathways (activated by infection, promotes upregulation of anti-viral proteins and apoptosis)
What are the most common causes of the common cold?
- rhinovirus
- coronaviruses
- influenza
What are serotypes?
pathogens that cannot be recognised by serum (antibodies) that recognise another pathogen
What is antibody mediated immunity?
humoral immunity
- adaptive, dependent on prior exposure
- B cells differentiate into antibody secreting plasma cells
- different antibody classes have different biochemical properties and functions
What are the characteristics of RSV?
- nasal flaring
- chest wall retractions
- hypoxemia and cyanosis
- croupy cough
- expiratory wheezing, prolonged expiration
- tachypnea
What is the impact of RSV and its paediatric burden?
- leading cause of infant hospitalisations
- recurrent re-infection
- no vaccine
- 1% develop severe bronchitis
- all children infected by age 3
What are the treatment options for viral respiratory infections?
- supportive therapy
- preventative/prophylactic
- therapeutic
What are the different types of vaccines?
- major surface antigen (spike protein)
- viral vector
- mRNA vaccine
What are the different therapeutic options for viral respiratory infections?
Anti-inflammatory - Dexamethasone (steroids) - Tocilizumab (anti-IL6R) - Sarilumab (anti-IL6) Anti-virals - Remdesivir (broad spectrum) - Paxlovid (anti-viral protease inhibitor) - Casirivimab and Imdevimab (monoclonal neutralising)
What are the different supportive therapies available for viral respiratory tract infections?
- oxygen (hypoxia)
- fluids (dehydration)
- analgesia (pain)
- nebulised saline
- chest physiotherapy
What is the interplay between viral and bacterial infections?
high likelihood of simultaneous viral and bacterial infections
What are the common bacterial causes of respiratory infection?
- Streptococcus pneumoniae
- Myxoplasma pneumonia
- Haemophilus influenzae
- Mycobacterium tuberculosis
What are the common viral causes of respiratory infection?
- Influenza A or B virus
- Respiratory Syncytial Virus
- Human metapneumovirus
- Human rhinovirus
- Coronaviruses
What is commensal bacteria?
microbes that live in a symbiotic relationship with their host
What are the risk factors of developing RSV bronchiolitis in infants?
- premature birth
- congenital heart and lung disease
What respiratory infection causes the highest annual mortality in the average year?
Mycobacterium tuberulosis
At what age do humans experience the most frequent respiratory infections?
0-10 years old
What is the frequency and severity of an upper respiratory tract infection?
Low severity, high frequency
What is the frequency and severity of a lower respiratory tract infection?
Moderate severity and frequency
What is the frequency and severity of pneumonia
High severity, low frequency
How do respiratory tract infections rank in global causes of death and DALYs?
- 4th highest cause of death
- 1st in global DALYs
What are the demographic and lifestyle risk factors for pneumonia?
Age <2 years or >65 years
Cigarette smoking
Excess alcohol consumption
What are the social risk factors for pneumonia?
Contact with children aged <15 years
Poverty
Overcrowding
Which medications are risk factors for pneumonia?
Inhaled corticosteroids
Immunosuppresants (e.g steroids)
Proton pump inhibitors
What risk factors for pneumonia are found in a patient’s medical history?
COPD, Asthma
Heart disease
Liver disease
Diabetes mellitus
HIV, Malignancy, Hyposplenism
Complement or Ig deficiencies
Risk factors for aspiration
Previous pneumonia
Which risk factors for pneumonia are specific to certain pathogens?
Geographical variations
Animal contact
Healthcare contacts
Which causative agent is most likely to cause a pandemic?
Influenza A
What are the key characteristics of streptococcus pneumoniae?
Gram-positive, extracellular, opportunistic pathogen
What are the typical pneumonias?
- Streptococcus pneumoniae
-Haemophilus influenzae - Moraxella catarrhalis
- most common
What does pneumonia lead to in lungs?
- lung injury
- arterial hypxemia
- ARDS
How does pneumonia lead to sepsis?
- bacteraemia and systemic inflammation cause organ infection and injury/dysfunction
- treatment can also cause this
Which antibiotics are used to treat bacterial pneumonia?
- penicillins e.g amoxixillin
- macrolides e.g. clarithromycin
- broad spectrum antibiotics
How do penicillins work?
beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation
How do macrolides work?
bind to the bacterial ribosome to prevent protein synthesis
What can cause absence of prior immunity?
- innate immunodeficiency
- insufficient B cell and T cell response
Which predisposing conditions can lead to severe disease?
Frail elderly
COPD/asthma
Diabetes
obesity
pregnancy
Where do viruses which have existed in humans for a long time prefer to bind?
Cells of the upper respiratory tract
What does influenza A bind?
Haemogglutinin binds to sialic acid
What does SARS-CoV-2 bind?
Spike protein binds to ACE2
Which immunoglobulin is the upper respiratory tract enriched for?
IgA
Which immunoglobulin are the lungs enriched for?
IgG
What is viral bronchiolitis associated with?
Development of asthma
Which virus is the most common cause of asthma and COPD exacerbations?
Rhinovirus