Respiratory Infections Flashcards
What are the symptoms of upper respiratory tract infections?
- cough
- sneezing
- runny/stuffy nose
- sore throat
- headache
What are the symptoms of lower respiratory tract infections?
- ‘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 DALY?
Disability-Adjusted Life Year
–> sum of Years of Life Lost (YLL) + Years Lost to Disability (YLD)
What are the ‘common’ causative agents of respiratory infection?
bacterial:
- streptococcus pneumoniae
- myxoplasma pneumoniae
- haemophilus influenzae
- mycobacterium tuberculosis
viral:
- influenza A or B
- respiratory syncytial virus
- human metapneumovirus
- human rhinovirus
- coronavirus
What are some bacterial species that cause community acquired pneumonia (CAP)?
- streptococcus pneumoniae (40-50%)
- myxoplasma pneumoniae
- staphylococcus aureus
- chlamydia pneumoniae
- haemophilus influenzae
What are some bacterial species that cause hospital acquired pneumonia (HAP)?
- staphylococcus aureus
- pseudomonas aeruginosa
- klebsiella species
- E.coli
- acinetobacter spp.
- enterobacter spp.
What are some bacterial species that cause ventilator associated pneumonia?
- pseudomonas aeruginosa (25%)
- staphylococcus aureus (20%)
- enterobacter
What are examples of typical pneumonias?
- streptococcus pneumoniae
- haemophilus influenzae
- moraxella catarrhalis
What are examples of atypical pneumonias?
- mycoplasma pneumoniae
- chlamydia pneumoniae
- legionella pneumophilia
^difficult to culture bc slower growing and may be intracellular
What are the different outcomes of pneumonia?
- lung injury leading to ARDS (acute respiratory distress syndrome)
- bacteremia–>sepsis
- systemic inflammation
- -> organ damage
- treatment side effects e.g. ventilator induced injury
How do you treat bacterial pneumonia?
1st step= supportive therapy:
- oxygen for hypoxia
- fluids for dehydration
- analgesia for pain
- nebuliser saline to help clear mucus
antibiotics
Why are HAPs treated differently to CAPs with regards to antibiotics?
many are drug resistant, so higher levels of different ABs are required
Why is the treatment regime slightly different depending on whether bacteria is typical or atypical?
because of the intracellular lifestyle and longer replication cycle of many atypical bacteria
N.B. typical CAPs may respond to penicillins and atypical CAPs to macrolides
What is the key to increasing the success of antibiotics?
- time to administration–> for every hour in septic shock, survival reduces by 7.9%, so the sooner you can limit bacterial replication, the greater chance of survival
- using an effective AB–> often penicillins and macrolides are given at same time, as it can take long to get microbiological test results
Do you catch pneumonia or spontaneously acquire it?
both
e.g. strep. pneumoniae, haemophilus influenzae, and staph. aureus are commonly found in large abundance in upper respiratory tract and nose of healthy individuals w/ no symptoms (live as part of microbiome)
BUT some are
What is an opportunistic pathogen?
a microbe that doesn’t generally cause infectious disease, but takes advantage of a change in conditions (often immunosuppression)
What is a pathobiont?
a microbe that is normally commensal, but if found in wrong environment / anatomical site can cause disease
e.g. bacterium normally found in intestine making its way into respiratory tract, where it might proliferate and cause inflammation, as not tolerated
What are the risk factors for active TB?
- HIV (18 fold)
- alcohol consumption (3.3 fold)
- smoking (1.6 fold)
N.B. high prevalence of latent TB in community
What is the standard treatment for TB?
combination of 4 antibiotics for 6 months
–> concern about multi drug resistant TB (commonly to rifampicin)
What is a serotype?
a virus that is recognised uniquely by the immune system- generates a unique set of antibodies
Why do viral infections result in disease?
- -> replication and lysis damages respiratory epithelium, leading to:
- loss of cilia, allowing bacterial growth
- damaged barrier integrity, preventing oxygen transfer and causing microedema
- -> viral infection results in substantial immune responses, leading to cellular inflammation and inflammatory mediator release
N.B. early stages- often damage caused by virus itself, then in later stages- often immune response that causes symptoms
Why does avian flu (H5N1) cause very severe disease, but struggle to transmit in humans?
its haemogglutinin binds alpha 2,3 sialic acids, which are primarily located in lower respiratory tract (v. low frequency in upper respiratory tract)
How can we explain the pattern of nasal followed by lower respiratory tract illnesses that people display with SARS-CoV-2?
- spike protein binds to ACE2 (receptor)
- ACE2 primarily found in nasal epithelium
- seen throughout respiratory tract, but highly expressed in type 2 pneumocytes (in lungs)
- ACE2 upregulated in smokers (explains risk factor?)
Why do rhinoviruses more rarely cause severe disease?
- major group bind ICAM-1 and minor group bind low density lipoprotein family of receptors
- both^ primarily in upper respiratory tracts, esp. nasopharynx
Why does H1N1 influenza A (swine flu) primarily cause disease in the upper respiratory tract?
its haemagglutinin on its surface binds alpha 2,6 sialic acids, which are expressed primarily in the upper respiratory tract
Why can RSV (respiratory syncytial virus) be found in almost all parts of the respiratory tract?
its F and G proteins bind glycosaminoglycans, which are expressed in receptors like IGF1 and nucleolin- roughly distributed throughout the lungs
How many serotypes of RSV are there?
2: A and B
What factors regulate the outcome of a respiratory virus infection?
- highly pathogenic strains (zoonotic)
- absence of prior immunity: innate immunodeficiency (e.g. IFITM3 gene variant), specific immunity or cross reactivity in B or T cell compartment
- risk factors / predisposing illness/conditions: frail elderly, diabetes, obesity, pregnancy, COPD/asthma
What are interferons (IFN)?
- family of cytokines
- 3 groups: type I (IFN-alpha, IFN-beta), type II (IFN-gamma), type III (IFN-lambda)
- named for ability to ‘interfere’ with viral infection in vitro
- produced by infected host cells or immune cells very rapidly and early
- signal on interferon receptors to induce interferon stimulated genes (ISGs)–> can directly inhibit viral replication inside a cell
How might interferons be important in dictating your response to SARS-CoV-2?
there is a much higher frequency of loss of function mutations in IFNAR1, IRF7, TLR3 genes (all involved in interferon signalling) in individuals suffering life threatening disease compared to those suffering mild disease or asymptomatic
What are the signs and symptoms of RSV infection in infants?
- wheezing
- prolonged expiration
- coughing
- hypoxemia and cyanosis
- nasal flaring
What are the risk factors for severe RSV disease?
- premature birth
- congenital heart and lung disease
What are the treatment options for RSV?
- monoclonal antibodies may be given prophylactically to at risk infants during RSV season to limit severe disease
- broad spectrum antivirals (not much therapeutic benefit)
- supportive treatment e.g. oxygen
- NO VACCINE available
