respiratory tract infection Flashcards
potential evolution line of a resp tract infection?
upper respiratory tract infection (cough sneezing runny nose sore throat and headache) → lower resp tract infection (a productive cough muscle aches wheezing breathlessness fever and fatigue) → pneumonia (chest pain blue tinging of lips severe fatigue and high fever)
which is worse - upper or lower tract infections?
lower → among the leading causes of death in the world
what factor has a significant effect on mortality burden?
age
risk factors for pneumonia?
- demographic/lifestyleage under 2 or 65+cigarette smoking, excess alcohol
- social factorsclose contact with children <15 and overcrowding, poverty
- medicationsinhaled corticosteroidsimmunosuppressantsPPIs
- medical historyCOPD, asthma, DM, heart/liver diseaseHIV, malignancy, hyposplenismcomplement/Ig deficienciesaspiration risk factorsprevious pneumonia
geographical variation,animal contect,healthcare contact
common causative agents for resp infections?
- bacterialstreptococcus pneumoniaemycoplasma pneumoniaehaemophilus influenzaemycobacterium tuberculosis
- viralinfluenza A/Brespiratory syncytial virushuman metapneumovirusrhinoviruscorona viruses
differences in common causative agents in CAP and HAP?
community acquired → strep pneumoniae, mycoplasma pneumoniae,haemophilus influenza,staph.aureus,chlamydia pneumonia
say my surname child
hospital acquired → staph aureus, pseudomonas aeruginosa,klebsiella species,E coli,acinetobacter spp,enterobacter spp
she pretends kids eat all eggs
ventilator acquired–>
pseudomonas areuginosa
staphylococcus aureus
enterobacter
subtypes of acquired pneumonia?
typical vs atypical
typical → common bacterial species eg streptococcus pneumonia,haemophillus influenza and moraxella catarrhalis. SMH
atypical → more distinct species, slower onset of symptoms, milder eg mycoplasma pneumonia,chlamydia pneumonia,legionella pneumophilia MLC. also have walking pneumonia .They are more difficult to culture so might need a different abx regime
what is the difference in treatment? pneumoonia subtypes
typical = often penicillin eg amoxicilin beta lactams that bind protein in the bacterial cell wall to prevent transpeptidation
atypical = often penicillin + macrolides eg clarithromycin bind to bacterial ribosomes to prevent protein synthesis
how is potential bacterial pneumonia graded?
use CRB-65 / CURB-65 scoring
1 point for each of:
confusion, resp rate > 30, blood pressure under 90 syst and/or 60 dias, 65 yo or older
in hospital: urea over 7 mmol/L
CURB-65 scoring boundaries
0 = low severity, 1-2 = moderate severity (consider hospital), 3-4 = high severity (urgent hospital, empirical antibiotics if life threatening)
bacterial pneumonia treatment?
supportive therapy → oxygen, fluids, analgesia,neubulised saline and chest physio?
antibiotics → penicillins, macrolides
what is an opportunistic pathogen?
microbe that takes advantage of a change in conditions e.g. immunosuppression to cause infection
what is a pathobiont?
microbe that is normally commensal but can cause illness if found in the wrong place
factors that can cause variable disease outcomes?
specific strains of causative agent, absence/presence of prior host immunity, predisposing illnesses and conditions
where in the respiratory tract do viruses tend to infect?
if virus has existed in humans for a long time → adapt to preferentially target cells in upper resp tract
defence mechanisms of the respiratory epithelium?
tight junctions
mucous lining and cilial clearance
antimicrobials, pathogen recognition receptors, interferon pathways
what are serotypes?
different serotypes = can’t be recognised by same serum/antibody
antibody distribution in respiratory tract?
upper → high frequency of IgA plasma cells. Dimeric not inflammatory and protease resistant
lower → enriched for IgG - thin alveolar walls allows transfer of plasma IgG into alveolar space. Smaller ,Covid vaccine generated large amounts of this tor deuce severity
what is RSV?
respiratory syncytial virus
characteristics of infection?
repeated infection by similar strains possible
in what subset of the population is it particularly prevalent?
babies → almost all children have had it by age 3
what does RSV cause
1% - severe bronchiolitis
croupy cough, hypoxemia and cyanosis, expiratory wheeze, tachypnea with apneic episodes, chest wall retraction
risk factors of rsv
premature birth, congenital heart and lung disease
SARS-CoV-2 treatment options?
supportive → oxygen, fluids, analgesia
prophylactic → vaccine
therapeutic → anti-inflammatory e.g. dexamethasone
antivirals → remdesivir broad spectrum, monoclonal antibodies possible, paxlovid an antiviral protease inhibitor,casirivimab and imdevimab (monoclonal antibodies)
features of interplay between bacterial, viral and chronic lung diseases?
viral bronchiolitis → asthma development association
rhinoviruses (and other transient infections) can cause exacerbations of chronic disease like COPD, asthma
high likelihood of secondary bacterial pneumonia after viral resp infection
ventilator associated pneumonia
pseudomonas aeruginosa
staphylococcus aureus
enterobacter
why do viral infections cause disease
epithelial damage leads to loss of cilia,reduced barrier integrity,bacterial growth
leads to airway narrowing
fluid and mucus build up in airways and parenchyma
damage to gas exchange surfaces
serotypes
viruses which cant be recognised by serum that recognise another virus-implications for protective immunity
IFN-I
important role in viral infection
inhibits viral replicstion and activates antiviral state
innate immunity
alveolar macrophages-phagocytosis,tissue homeostasis and pathogen sensing
resident dendritic cells-respond to inflammation and take up and present foreign antigen driving adaptive immune response
neutrophils-main cell type recrutied upon infection,can cause inflammatory damage
NK cells-provide innate antiviral immunity against infected cells
monocytes-resukts into site to provide mediators and macrophage sources
antibody mediated immunity
humoral immunity
adaptive so dependant on prior exposure
b cells activated to differentiate into antibody secreting plasma cells
different antibody classes provide different biochemical properties and function
Where do influenza bird flu rhinovrius and Covid bind
Influenza A:haemagluttinin binds to alpha 2,6 sialic acid
Bird flu (H5N1 avian flu): haemaglutinin binds to alpha 2,3 sialic acid (common in lower resp tract)
Covid:spike proteins bind to ACE2 high in pneumocytes and nasal epithelium and increased expression in smokers
common cold rhinoviruses: bind to ICAM-1 (major group) and LDLR (minor group)
Treatment for CAP with respect to CURB-65
Treat the patient for 5-7 days for typical pneumonia, and 7-14 days for atypical
- 0 ⇒ Amoxicillin (or clarithromycin / doxycycline if allergic to penicillin)
- 1-2 ⇒ Amoxicillin AND clarithromycin (replace amoxicillin with doxycycline if allergic)
- 3-5 ⇒ Benzylpenicillin IV with oral clarithromycin (replace benzyl with teicoplanin if allergic)
Treatment for HAP with respect to CURBx 65
Treat for 5-7 days
0 ⇒ NOT severe so treat with oral doxycycline
1-2 ⇒ NOT severe so treat with oral doxycycline
3-5 ⇒ SEVERE so treat with tazocin (piperacillin-tazobactam) IV, with or without gentamicin IV
asthma as a riskfactor for pneumonia
Exacerbations are the most common cause of hospitalisation
resp infections specifically viral are the major cause of exacerbations
Hospitalisations due to exacerbations are the major predictor of asthma mortality
severe exacerbations are less common
how does acute bacterial pneumonia cause damage
bronchilitis which is inflammation and swelling of bronchi
bronchiolitis which is inflammation and swelling of the bronchioles
pneuomnia which is inflammtion and swelling of the alveoli
pneuomnia mechanism of action
lung injury causes arterial hypoxemia which leads to ARDS or organ injury and dysfunction causing sepsis or deterioration
bacteremia causes organ infection which causes organ injury or dysfunction leading to sepsis or deterioration
systemic inflammation causes organ dysfunction leading to sepsis or deterioration
treatment can also lead to deterioration
commensal bacteria and pneumonia
oropharynx contains haemophillus,staph aureus and strep pneumonia
nose contains staph aureus and strep pneuomnia
These commensal bacteria can become opportunistic and cause pneumonia if your immune system weakness,hospitalisation and viral infections
physical and chemical barriers of the resp epithelium
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.
antibodies present
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
Enriched for IgGs
Thin-walled alveolar space allows transfer of plasma IgGs into the alveolar space
serotypes of rhinovirus influenza rsv and sars cov2
rhinovirus
100-300+ different serotypes within RV-A, B and C strains.
Long lasting antibody mediated immunity.
influenxa
No re-infection by same strain
Influenza strains ”drift” and ”shift” surface antigens (HA, N) to avoid antibody mediated immunity
rsv
Recurrent infection with the same serotype/strain.
Limited mutation of surface antigens. (F, G).
Natural antibodies wane rapidly allowing re-infection.
sars cov2
Antigenically novel coronavirus.
No prior exposure.
Antibodies wane over time.
Some evidence of surface antigen mutation
treatment for sars cov2
supportive therapy
oxygen,fluids,analgesia,nebulied saline,chest physio?
preventative/prophylatic
vaccines,major surafce antigen (spike protein),viral vector eg adenovirus vaccine or mrna vaccines
therapeutic
anti inflammatory eg dexamethasone (steroid) and tocolizumab (anti IL6R) or sarilumab (anti il6)
anti virals
remdesivir which is a broad spec antivrial and blocks rna dependant rna polymerase activity
paxlovid which is an antiviral protease inhibitor
casirivimab and imdevimab which is a monoclonal neutralising antibody for sars cov 2
interplay of viral infections with chronic lung disease
viral bronchiolitis is associated with the development of astma
rhinovrius is the most common cause of asthma and copd
high likelihood of secondary bacterial pneumonia after viral infecion
