respiratory tract infections Flashcards
what is the epidemiology of respiratory tract infections?
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
what are the different types of respiratory tract infections?
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
what is the health burden of RTIs?
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
what are the risk factors for pneumonia?
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
what are the causative agents of respiratory infections?
bacterial
viral
what are the main bacteria that cause RTIs?
Streptococcus pneumoniae
Mycoplasma pneumoniae
Haemophilus Influenzae
Mycobacterium tuberculosis
what are the main viruses that cause RTIs?
Influenza A or B virus Respiratory Syncytial Virus Human metapneumovirus Human rhinovirus Coronaviruses
what are some facts about COVID-19
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
what is community acquired pneumonia (causes)?
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
what is hospital acquired pneumonia (causes)?
bacterial: Staphylococcus aureus Psuedomonas aeruginosa Klebsiella species E. Coli Acinetobacter spp. Enterobacter spp.
Ventilator associated pneumonia:
Psuedomonas aeruginosa (25%)
Staphylococcus aureus(20%)
Enterobacter
what are typical vs atypical pneumonias?
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
what are the mechanisms of damage in acute bacterial pneumonia?
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
how is bacterial pneumonia graded?
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
how is bacterial pneumonia treated?
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
can you catch pneummonia?
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
why do viral infections result in disease?
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
what causes severe disease?
- Highly pathogenic strains (zoonotic)
- Absence of prior immunity -
Innate immunodeficiency
B cells
T cells - Predisposing illness/conditions -
Frail elderly
COPD/asthma
Diabetes, obesity, pregnancy etc.
what is virus tropism?
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
how do epithelial cells act as the first line of defence?
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.
what is a serotype?
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
what do serotypes tell us about viral immunity?
(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
what is RSV broncholitis like in children?
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
what are possible treatments for viral RTIs?
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
what is the interplay between viral and bacterial infections?
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?
