Lecture 9: Resp tract infections Flashcards
What are some features of innate immunity?
Cilia – mucociliary escalator removing debris and pathogens
Alveolar macrophages:
- secrete antimicrobials
- engulf and kill pathogens
- recruit other immune cells
- process and present antigens to T cells
What are some features of acquired immunity?
B cell/T cell responses- essential for intracellular pathogens, such as mycobacteria, viruses and fungi
IgA secreted by plasma cells interferes with adherence and viral assembly
What are the macro responses to infection and inflammation?
Redness Swelling Heat Pain Loss of function
What are the micro responses to infection and inflammation?
Vasodilation
Increased vascular permeability
Inflammatory cell infiltration
How many colds do preschool children get per year?
5-7
How many colds do adults get per year?
2-3
What % of all time lost from work is accounted for by colds?
40%
How many viral subtypes are associated with colds?
> 200
What % of colds are caused by rhinovirus?
30-50% (most common cause)
What % of colds are caused by human coronaviruses?
10-15%
What is the form of transmission for viral URTIs?
Hand contact: virus remains viable for up to 2 hours on skin or several hours on surfaces
Droplet transmission from sneezing / coughing / breathing
What is the incubation period of the common cold?
2-3 days
How long do symptoms of the common cold last?
3-10ds, and up to 2 weeks in 25% patients
What causes intranasal a sore throat and nasal congestion due to vasodilation?
Bradykinin
What causes sneezing, mediated by stimulation of the trigeminal sensory nerves?
Histamine
What causes nasal discharge (snot) to change colour with increasing numbers of neutrophils?
Myeloperoxidase
What causes a cough?
The vagus nerve – inflammation has to extend to the larynx to trigger this; hyper-reactive response in URTI
What are the key features of a cold?
Appears gradually
Affects mainly your nose and throat (coryza)
Makes you feel unwell but you’re okay to carry on as normal – for example, go to work
Usually no fever
What are the key features of the flu?
Appears quickly within a few hours
Affects more than just your nose and throat
Makes you feel exhausted and too unwell to carry on as normal
High fevers
May have lower resp tract features
What is the incubation period of the flu?
1-4 days
What are the symptoms of the flu?
Abrupt onset of fever+
cough, headache, myalgia and malaise, sore throat, nasal discharge
Acutely debilitating.
Fever 38-41OC; otherwise examination often unremarkable
What are the risk factors for complications of the flu?
Immunosuppression or chronic medical conditions
Pregnancy or 2 weeks postpartum
Age <2y or >65y
BMI >40
What are the complications of the flu?
Primary viral pneumonia
Secondary bacterial pneumonia
CNS disease
Death (estimated mortality rateamong people infected withinfluenzain the US is about 0.13percent)
What are the 3 problems a virus must solve to be successful?
It must know how to replicate inside a cell
It must move from one infected cell to a new cell (and a new host) in order to persist in nature
It must develop mechanisms to evade host defences
What is haemagglutinin?
Influenza surface protein that binds sialic acids on cell surface glycoproteins and glycolipids in the respiratory tract.
What is neuraminidase?
Influenza surface protein that allows the virus to escape by cleaving sialic acid bonds – otherwise the escaping virions all clump together
What is distinctive about the influenza virus genome?
Segmented genome (8 parts) so can reassort if 2 different viruses infect the same cell
How many segments are there to the influenza virus genome?
8
What is viral drift?
RNA has no proof reading mechanism so accumulates mutations
What is viral shift?
Undergoing drift but then experience a large mutation (entire section of genome is changing)
What are the options for treatment and prevention of influenza?
Active immunisation - against H and N components
Tamiflu = a neuaminidase inhibitor
Hand hygiene and droplet precautions
What is pneumonia?
Infection of the lung parenchyma
What are the signs and symptoms of pneumonia?
Fever
Breathlessness
Cough
Sputum production
Hypoxia
Increased respiratory rate
Pleuritic chest pain
Sepsis
What would be seen on the CXR of someone with pneumonia?
Consolidation - alveoli and bronchioles completely filled with inflammatory debris / pus / pathogens
Heart borders or diaphragm obscured due to loss of solid-gas interface
Air bronchograms - air in larger bronchi outlined by surrounding consolidation
What are the CAP pathogens?
Streptococcus pneumoniae
Haemophilus influenzae
Mycoplasma pneumoniae
Legionella pneumophila
Staphylococcus aureus
What are the risk factors for S.pneumoniae infection?
Alcoholics Respiratory disease Smokers Hyposplenism Chronic heart disease HIV
What pathogen is the most common cause of CAP?
S.pneumoniae
What are the features of S.pneumoniae?
Gram positive cocci
Acquired in nasopharynx
Asymptomatic carriage in 40-50%
smokers>non-smokers
Prevention – vaccine
Treatment – penicillin
What are the features of M.pneumoniae?
Classically young patient, vague constitutional upset, several weeks
Extrapulmonary symptoms very common
Lacks cell wall
- resistant to penicillins
- cannot grow on normal lab plates
Diagnosis by PCR of throat swab (VTS)
Treatment: macrolides or tetracyclines
Which organism is the most common cause of ambulatory ‘atypical pneumonia’?
M.pneumoniae
What are the features of L.pneumonophila?
Sporadic infection or in outbreaks associated with a contaminated water source
Uncommon
Can cause severe, life threatening infection
RFs= smoking and chronic lung disease
Diagnosis
Don’t grow on routine culture – need special conditions, and longer
Urinary legionella antigen
Treatment: macrolides or quinolones
What are the risk factors for L.pneumonophila?
Smoking and chronic lung disease
What is HAP?
Definitions vary - new onset at least >48 hours since admission
Hospitalised patients become colonised
with hospital bacteria
May either be intrinsically more resistant to antibiotics, or have acquired resistance mechanisms
Broader spectrum antibiotics are used empirically
How much of the worlds population has latent TB?
One quarter
What % of UK TB cases were born outside the UK?
71%
rates 13x higher than if born in the UK
What % of people with TB have a social risk factor?
12%
What % of people with TB are co-infected with HIV?
2.8%
What are the features of TB pathogen?
Aerobic bacillus
Divides every 16-20 hours (slow) – lab extends culture to 56 days
Cell wall, but lacks phospholipid outer membrane
Does not stain strongly with Gram stain (weakly positive)
Retains stains after treatment with acids
Referred to as acid fast bacillus (AFB)
What are the special strain required in TB?
Ziehl-Neelsen or auramine-rhodamine
What is the pattern of TB infection?
Initiated by the inhalation of aerosol droplets that contain bacteria
The initial stages of infection characterised by innate immune responses - involve the recruitment of inflammatory cells to the lung
Dissemination to the draining lymph node, dendritic cell presentation of bacterial antigens leads to T cell priming and triggers an expansion of antigen-specific T cells, which are recruited to the lung
The recruitment of T cells, B cells, activated macrophages and other leukocytes leads to the establishment of granulomas
What % of infections become progressive primary TB?
5%
What % of infections become latent TB?
95%
What % of latent infections reactivate?
5%
20x higher if HIV or transplant; 2-3x higher if IVDU, diabetes, smoker
What are the features of latent TB?
Dormant bacilli
Contained by host defences
Non-infectious
Asymptomatic
Dx by demonstrating host IR
What are the features of active TB?
Actively replicating bacilli
May be infectious (site-dependent)
Symptomatic (site-dependent)
Dx by isolating AFBs, growing MTB or PCR positive
