Respiratory Infections Flashcards
How can a cold develop into pneumonia?
Starts off as an upper resppiratory tract infection
Develops into a lower respiratory tract infection e.g. bronchitis, bronchiolitis
Untreated, progresses to pneumonia
What are the signs and symptoms for:
Upper respiratory tract infection
Lower respiratory tract infection
Pneumonia
Upper = coughing, sneexing, stuffy nose, sore throat, headache
Lower = phlegm, more ‘productive’ cough, wheezing, muscle aches, breathlessness, fever, fatigue
Pneumonia = chest pain, reduced oxygenation of blood, cyanosis, severe fatigue, high fever
What is DALY?
Disability-adjusted Life Year = sum of years of life lost and years lost to disability
Why do acute lung infections only rank 4th in global deaths but 1st in global DALYs?
Acute respiratory infections are seen in the elderly all over the world
But they are also seen in infants under the age of 5 in certain parts of the world i.e. Africa, South Asia = greater infant mortality from acute resp infections
What risk factors affect the development of pneumonia?
Age (<2 or >65yrs) v. important
Cigarette smoking
Excess Alcohol consumption
Contact with children <15yrs
Poverty
Overcrowding
Medications e.g. inhaled corticosteroids, immunosuppresants, proton pump inhibitors
Medical History e.g. COPD, asthma, heart disease, liver disease, DM, HIV, malignancy, complement / Ig deficiencies, risk factors for aspiration, previous pneumonia
Geographical variations, animal contact, healthcare contacts
What causes respiratory illnesses?
Mix of bacterial and viral respiratory illnesses
Leads to a mix of bronchiolitis and pneumonia
What are common bacterial and viral causative agents for respiratory tract infections?
Bacterial: Streptococcus pneumoniae Myxoplasma pneumoniae Haemophilus Influenzae Mycobacterium tuberculosis
Viral: Influenza A or B virus Respiratory Syncytial Virus Human metapneumovirus Human rhinovirus Coronavirus
Do we always know what pathogen is causing the respiratory tract infection?
No
It is often a mix of bacterial and viral infections, with no singular dominant pathogen
Which respiratory infection causes the highest annual mortality?
Mycobacterium tuberculosis
What is the most commonly identified pathogen in individuals with respiratory illness?
Rhinovirus
How does the cause of pneumonia differ?
Pathogen causing the pneumonia depends usually on where the pneumonia was picked up from: i.e. community, hospital or ventilator
What pathogens cause community acquired pneumonia?
Community acquired = most common cause of pneumonia
Pathogens (bacterial):
Streptococcus pneumoniae (40-50%) Myxoplasma pneumoniae Staphylococcus aureus Chlamydia pneumoniae Haemophilus Influenzae
What are the features of streptococcus pneumoniae?
Gram-positive
Extracellular
Opportunistic pathogen
Adhesion molecules on the streptococcus pneumoniae bind to the epithelium lining of the respiratory tract = allows them to absorb nutrients from the extracellular environment
What pathogens cause hospital acquired pneumonia?
Staphylococcus aureus Psuedomonas aeruginosa Klebsiella species E. Coli Acinetobacter spp. Enterobacter spp.
What pathogens cause ventilator acquired pneumonia?
Psuedomonas aeruginosa (25%) Staphylococcus aureus(20%) Enterobacter
How is ventilator acquired pneumonia reduced?
Give patients on ventilator antibiotics to prevent infection and pneumonia
What are typical bacterial pneumonias?
What are some examples of typical pneumonia causative agents?
More sudden onset, more serious illness
Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis
What are atypical bacterial pneumonias?
What are some examples of typical pneumonia causative agents?
Milder, often slower-growing, can be and more persistent; may be intracellular = not culturable
Mycoplasma pneumoniae, Chlamydia pneumoniae,
Legionella pneumophilia
Does it matter if the pneumonia is caused by typical or atypical bacteria?
Yes - results in different treatment regimes
What are the consequences of acute bacterial pneumonia?
Inflammation and fluid buildup in the aveolar spaces where gas exchange occurs - reduces gas exchange
Pneumonia can lead to:
- Lung injury –> acute respiratory distress syndrome
- Bacteremia —> organ infection –> organ injury / dysfunction
- Systemic inflammation –> pronounced inflammation and damage to the lungs
- Treatment itself can lead to side effects e.g. ventilators causing lung injury
These can all lead to SEPSIS and deterioration
What treatment options are available for bacterial pneumonia?
- Supportive Therapy:
- Oxygen delivery (for hypoxia)
- Fluid (for dehydration)
- Analgesia (for pain) - Antibiotics:
- Penicillins e.g. amoxicillin - beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation and so inhibit cell wall synthesis (only effective against gram positive bacteria)
- Macrolides e.g. clarithromycin - bind to the bacterial ribosome to prevent protein synthesis
How does antibiotic dosage and duration differ between community and hisptial acquired, and between typical or atypical?
More severe the infection, the stronger the dose and the greater number of antibiotics the patient is on
5-7 days for typical community acquired
7-14 days for atypical community acquired
5-7 days for hospital acquired
What is the key to increasing the success of antibiotics?
Time of administration - limit bacterial replication = greater chance of survival
Using and effective antibiotic - e.g. atypical community acquired bacteria require macrolides and penicillin is not effective
How is pneumonia spread / caught?
Many of the bacteria are a part of our microbiome e.g. strep. pneumoniae, haemophilus spp, staph aureus
Some are caught from the external environment
Define the terms:
Opportunistic pathogen
Pathobiont
Opportunistic Pathogen = a microbe that takes advantage of a change in conditions (e.g. immuno-suppression)
Pathobiont = a microbe that is normally commensal, but if found in the wrong environment (e.g. anatomical site) can cause pathology as that microenvironment is not adapted to that pathogen e.g. if a gastric bacteria makes its way to the respiratory tract - the bacteria is tolerated in the gut but not in the lungs
What is latent tuberculosis (TB)?
Mycobacterium tuberculosis - inactive version living in the lungs that is capable of replicating but is not
1 in 4 have latent TB
Most do not develop active TB
What are the risk factors for TB?
HIV = 18-fold Alcohol = 3.3-fold Smoking = 1.6-fold
What is an active mycobacterium tuberculosis (Mtb)?
Latent bacteria starts to reactivate
Causing proliferation of the bacteria and inflammation surrounding the bacteria
Inflammation spreads through the lungs and through the blood causing systemic inflammation / damage
Why is TB challenging to treat?
Latent Mtb has very distinct microbiology (v. thick cell wall highly resistant to uptake of molecules and degradation by external environment) and so is highly resistant to the immune system
Also difficult to treat due to extremely slow replication cycle esp. in latent TB
What is the treatment of mycobacterium tuberculosis (Mtb)?
Standard treatment = combination of 4 antibiotics over 6 month period
What are the different types of virus that cause the ‘common cold’?
And how many different serotypes (distinguishable strains) are there of each?
Rhinovirus - 100+ Coronaviruses - 2 Influenza viruses - 3 Parainfluenza viruses - 4 Respiratory synctial virus - 2 Adenovirus - 47 Enterovirus - 40+
Why do respiratory viruses cause disease?
- Viruses replication, lysis and damage to epithelium leads to: loss of cilia, bacterial growth, poor barrier integrity promoting oxygen transfer, and loss of chemoreceptors
- Immune responses can results in cellular inflammation
- Local immune memory
- Mediator release - alter function of the respiratory tract
What regulates which virus is most likely to cause severe disease?
Use H1N1 influenze A and H5N1 avian flu as examples:
H1N1 influenza A has haemogluttinin on its surface that binds to alpha2,6 sialic acids, which are found mainly in the upper but not really in the lower respiratory tract
Whereas, H5N1 avian flu has haemogglutinin on its surface that binds to alpha2,3 sialic acids, which are mainly found in the lower but not really the upper respiratory tract
The cells the virus can bind to and use as host cells for replication affect the severity of the disease the virus can cause
How does the SARS-Cov-2 cause disease?
The spike (S) protein on the SARs-Cov-2 virus binds to ACE2 (angiotensin converting enzyme 2), which is mainly found in the nasal epithlium and in the type 2 pneumocytes (in the lungs)
What increases the expression of the ACE2 receptors?
Upregulated in smokers - explains why smoking is a risk factor to developing disease from SARS-Cov-2
What receptor do the human rhinoviruses bind to?
Majorly bind to ICAM-1
Minorly bind to low density lipoprotein family of receptors
Both primarily in the upper respiratory tract - nasopharynx
What receptor do respiratory syncytial viruses (RSV) bind to?
F and G proteins on the RSV bind to glycosaminoglycans in receptors such as IGFR1 and nucleolin
Found in all parts of the respiratory tract
How does the influenza A virus and respiratory syncytial virus (RSV) differ?
Influenza A =
No re-infection by same strain
Imperfect vaccines - annual vaccination required, vaccine-induced immunity, homotypic immunity
RSV =
Recurrent re-infection with similar / same strain
No vaccine - poor immunogenicity, vaccine-enhanced disease, very active research field
Why do same viral strains cause different outcomes in patients?
Highly pathogenic strains are usually zoonotic due to absence of immunity
Immune deficiencies
Predisposing illnesses / conditions
What are interferons?
Directly produced by infected cells or by immune cells that can sense viral proteins
They are a family of cytokines that ‘interfere’ with viral infection in vitro
3 groups: type I (IFNalphas / IFNbetas), type II (IFNgamma), type III (IFNlamda)
How does RSV affect infants?
RSV = leading cause of bronchiolitis in infants and so leading cause of infant hospitalisation in developed worlds
What are the risk factors for infants getting ill from RSV?
Premature birth
Congital heart and lung disease
How does RSV present in infants clinically?
Chest wall retractions Nasal flaring Prolonged expiration Wheezing Coughing Hypoxemia Cyanosis Bronchiole obstructions - typical of bronchiolitis
How does age change the likeliness and type of viral respiratory infections a person gets?
Young and older individuals are at significant risk to RSV
Adults and older children tend to only get upper respiratory tract infections - milder
Young - bronchiolitis
Older children are the spreaders - infectious
Caring adults - repeated colds, rarely severe, transmitters
Old and infirm = major cause of progressive lung disease and winter deaths
What are the treatment options for respiratory viral infections?
Supportive:
Oxygen therapy
Preventative:
Vaccines
Anti-virals
Monoclonal antibodies (mainly prophylactic)
What are the similarities in RSV and influenza symptoms?
Primarily upper respiratory tract infections with some lower respiratory tract infections
What are the differences between RSV and influenza symptoms and viral load?
Emergence and peak of influenza symptoms faster than RSV
Faster viral replication of the influenza than RSV - therefore peak viral load earlier than RSV
Influenza = pre-selected for seronegativity (i.e. this person must not have encountered ths strain before)
RSV = not pre-selected for seronegativity (same strain can reinfect)
Why does RSV not require pre-selected seronegativity?
RSV antibodies produced from infection wane quickly
Unlike for influenza, which stays around for longer
This allows for re-infection
What other viruses display no need for pre-selected seronegativity?
Coronaviruses
Metapneumoviruses
What is the interplay between viral and bacterial infections?
Common for co-infections: i.e. both, viral and bacterial infections, within an individual
After viral infections, bacterial burdens also increase - espeiclally in smokers and COPD patients
