Respiratory Infection Flashcards
What are signs of an upper respiratory tract infection?
- A cough
- Sneezing
- A runny or stuffy nose
- A sore throat
- Headache
What are signs of a lower respiratory tract infection?
- A “productive” cough - phlegm
- Muscle aches
- Wheezing
- Breathlessness
- Fever
- Fatigue
What are the signs of pneumonia?
- Chest pain
- Blue tinting of the lips
- Severe fatigue
- High Fever
How common are respiratory infection?
- 5 million deaths annually between 1990 and 2015 (upper)
- 3 million deaths annually from acute lower respiratory infection
- More common death in Africa and SA
What is DALY?
Disability-adjusted Life Year
A sum of Years of Life Lost (YLL) and Years Lost to Disability (YLP)
What are demographic and lifestyle risk factors for pneumonia?
- Age <2 years or >65 years
- Cigarette smoking
- Excess alcohol consumption
What are the social factors that are risk factors for pneumonia?
- Contact with children aged <15 years
- Poverty
- Overcrowding
What are medications that are a risk factor for pneumonia?
- Inhaled corticosteroids
- Immunosuppresants (e.g steroids)
- Proton pump inhibitors
What is medical history that is a risk factor for pneumonia?
- COPD, Asthma
- Heart disease
- Liver disease
- Diabetes mellitus
- HIV, Malignancy, Hyposplenism
- Complement or Ig deficiencies
- Risk factors for aspiration
- Previous pneumonia
What is the specific risk factor for certain pathogens that increase risk factors for pneumonia?
- Geographical variations
- Animal contact
- Healthcare contacts
What types of pathogens cause respiratory illness?
- Mix of viral and bacterial
- pneumonia and broncholitis present in children
Can you detect what pathogen causes respiratory infection?
Yes but most don’t
What are the common causative bacterial agents?
- Bacterial
- Streptococcus pneumoniae
- Myxoplasma pneumoniae
- Haemophilus Influenzae
- Mycobacterium tuberculosis
What are the common viral causative agents?
- Influenza A or B virus
- Respiratory Syncytial Virus
- Human metapneumovirus
- Human rhinovirus
- Coronavirus
What is SARS-Cov-2?
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 2020
53 million cases – 1.5 million deaths
What are the community acquired pneumonia (CAP) bacterial agents?
- most common type of pneumonia
1. Streptococcus pneumoniae (40-50%)
2. Myxoplasma pneumoniae
3. Staphylococcus aureus
4. Chlamydia pneumoniae
5. Haemophilus Influenzae
What are the hopsital acquired bacterial agents?
- Staphylococcus aureus
- Psuedomonas aeruginosa
- Klebsiella species
- E. Coli
- Acinetobacter spp.
- Enterobacter spp.
What are the bacterial agents associated with ventilator associated pneumonia?
- Psuedomonas aeruginosa (25%)
- Staphylococcus aureus(20%)
- Enterobacter
- so if put on ventilator usually given antibiotics to
What are atypical bacteria pneumonia?
- Mycoplasma pneumoniae
- Chlamydia pneumoniae
- Legionella pneumophilia
What are typical bacteria pneumonia?
- Streptococcus pneumoniae 2. Haemophilus influenzae
- Moraxella catarrhalis
- easier to culture and identify e..g because atypical are slow growing and are mostly intracellular bacterial pathogens
What is it important to know if typical or atypical?
Change treatment regime
What type of bacteria is streptococcus pneumoniae?
- Gram-positive
- Extracellular
- Oppurtunistic pathogen
What is the difference between typical and atypical bacteria?
- 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
What is bronchitis?
inflammation and swelling of the bronchi
What is bronchiolitis?
inflammation and swelling of the bronchioles
What is pneumonia?
inflammation and swelling of alveoli - limit gas exchange
What can pneumonia lead to?
- Lung injury
- Bacteremia
- Systemic inflammation
- Treatment
What can lung injury lead to?
Arterial hypoxemia:
1. Organ injury / dysfunction
2. Acute respiratory distress
syndrome
What can bacteremia lead to?
organ infection:
1. Organ injury or dysfunction
What can systemic inflammation lead to?
organ injury or dysfunction
What can organ injury or dysfunction lead to?
- deterioration
- sepsis
What is deterioration?
decrements in pulmonary, cardiovascular, neuromuscular, hematologic, cognitive, psychologic, and other functions
What are examples of some supportive therapy for bacterial pneumonia?
- Oxygen (for hypoxia)
- Fluids (for dehydration)
- Analgesia (for pain)
- Nebulised saline (may help expectoration) - clear mucus
- Chest physiotherapy
How can penicillin help and work for bacterial pneumonia?
e.g. amoxicillin – beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation
How can macrolides help and work for bacterial pneumonia?
e.g. clarithromycin – bind to the bacterial ribosome to prevent protein synthesis
What is the key to increasing the success of antibiotics?
- Time to administration (for every hour in septic shock survival is reduced by 7.9%
- Using an effective antibiotic – typical CAPs may respond to penicillins, Atypical CAPs require macrolides
How do you treat bacterial pneumonia at CURB-65 0 for CAP?
Amoxicillin (or clarithromycin / doxycycline if pen.allergic)
How do you treat bacterial pneumonia at CURB-65 0 for HAP?
NOT SEVERE: doxycycline PO
How do you treat bacterial pneumonia at CURB-65 1-2 for CAP?
Amoxicillin + clarithromycin (or clarithro/doxy)
How do you treat bacterial pneumonia at CURB-65 1-2 for HAP?
N/A
How do you treat bacterial pneumonia at CURB-65 3-5 for CAP?
BenzylPenicillin IV + clarithro. PO (or teicoplanin + clarithro)
How do you treat bacterial pneumonia at CURB-65 3-5 for HAP?
SEVERE: tazocin (piperacillin - tazobactam) IV +/- gentamicin IV
What is the duration for CAP bacterial pneumonia?
5-7 days (7-14 days for atypicals)
What is the duration for HAP bacterial pneumonia?
5-7 days
What bacteria is found in oropharynx?
- Strep. viridans
- Coagulase neg. staph
- Veronella
- Fusiforms
- Treponena spp.
- Beta-haem. strep
- Haemophilus spp.
- Staph. aureus
- Strep. pneumoniae
What bacteria is found in nose?
- Coagulase neg. staph
- Haemophilus spp.
- Staph. aureus
- Strep. viridans
- Strep. pneumoniae
What is the human microbiome?
100 trillion microbial cells populate our bodies at every barrier surface
What is the microbiota?
Ecological communities of microbes found inside multi-cellular organisms
What are commensal?
Microbes that live in a “symbiotic” relationship with their host. Providing vital nutrients to the host in the presence of a suitable ecological niche
What is an opportunistic pathogen?
A microbe that takes advantage of a change in conditions (often immuno-suppression)
What is a pathobiont?
A microbe that is normally commensal, but if found in the wrong environment (e.g. anatomical site) can cause pathology
How common is latent TB?
Estimated that 1 in 4 people have latent TB
How many deaths are caused by TB?
- 10 million active TB cases per year
* 1.4 million deaths from TB in 2019
What are the risk factors for active TB?
- HIV (18-fold)
- alcohol (3.3 fold)
- smoking (1.6 fold)
Is latent TB resistant?
Latent Mtb is highly resistant to the immune system
What is the standard treatment of TB?
combination of 4 antibiotics for a 6 month period
How common is multidrug resistant TB?
(e.g. commonly rifampicin) accounted for 206,000 cases of TB in 2019, up 10% from 2018
Is there such a thing as a commensal respiratory virus?
No
What is a serotype?
Viruses. which cannot be recognized by serum (antibodies) that recognise another - implications for protective immunity
What does viral infection lead to?
- Mediator release
- Cellular inflammation
- Local immune memory
- Damage to epithelium
What does damage to epithelium lead to?
- Loss of cilia
- Bacterial growth
- Poor barrier to antigen
- Loss of chemoreceptors
What does the major group of human rhinovirus bind?
bind ICAM-1
What does the minor group of human rhinovirus bind?
low density lipoprotein family of receptors
Can you get reinfection by the same strain in influenza?
No
Can you get recurrent reinfection with similar stains in RSV?
yes (only 2 serotypes A and B)
What are the imperfect vaccine for influenza?
- Vaccine-induced immunity rapidly wanes
- Mainly homotypic immunity
- Annual vaccination required
Why is there no vaccine for RSV?
- Poor immunogenicity
- Vaccine-enhanced disease
- Very active research field
What does latent to active TB involve?
latent bacteria to reactivate causing bacteria to proliferate and inflammation surrounding that bacteria which can rupture causing inflammation to spread through your lungs and also cause systemic damage
Why does pneumonia usually affect elderly?
Movement into lower respiratory tract from other areas due to poor health
What binds in H1N1 influenza A?
Haemogglutinin binds 𝛂2,6 sialic acids which are
When are 𝛂2,6 sialic acids present?
expressed primarily in upper respiratory tract with decreasing concentration in lower respiratory tract
What does H5N1 avian flue bind?
Haemogglutinin binds 𝛂2,3 Salic acids
Where are 𝛂2,3 sialic acids present?
primarily located in lower respiratory tract with decreasing concentration in upper respiratory tract (why avian flu causes severe disease but struggle to transmit in humans)
What does SARS-CoV-2 bind?
Spike (S) protein binds Angiotensin converting enzyme 2 (ACE2)
Whereis ACE2 found?
- Nasal epithlium (a lot in smokers)
- In type 2 pneumocytes (a lot in smokers)
Where does respiratory Syncytial Virus (RSV) bind?
F and G proteins bind glycosaminoglycans in receptors like IGFR1 and nucleolin
Where are RSV receptors found?
distributed around the lungs (RSV all parts of respiratory tract)
What causes severe disease?
- Highly pathogenic strains (zoonotic)
- Absence of prior immunity
- Predisposing illness/conditions
What does absence of prior immunity mean?
- Innate immunodeficiency (e.g. IFITM3 gene variant)
- B cells (antibody- presumably local)
- T cells (correlate with peripheral levels?)
What are some predisposing illness/conditions?
Frail elderly
COPD/asthma
Diabetes, obesity, pregnancy etc.
What can host defence be provided by?
interferons
What are interferons?
- Family of cytokines
* Named for ability to “interfere” with viral infection
What are the 3 groups of interferons?
- type I (IFN-αs/IFN-βs)
- type II (IFN-γ)
- type III (IFN-λ)in vitro
How are interferons produced?
- directly by infected cells which sense virus through TLR3
- or by immune cells that can sense viral proteins by IRF7
- Production of interferons very rapidly and early on infection
- Interferons signal on those receptors e.g. type 1 signal through IFNAR 1/2
- To stimulate ISGs - inihibit viral replication in a cell
So what happens in upper respiratory tract infection?
epithelial cells upregulate ISGs to inhibit further viral replication
What immune compartment provides long term protection after vaccination and natural infection?
B cells
Why is RSV dangerous?
- 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.
What are similar viruses to RSV with lower prevelance?
hMPV and PIV
What are risk factor for RSV?
- Premature birth
* Congenital heart and lung disease
What are the symptoms of RSV?
- Nasal flaring
- Chest wall retractions
- Hypoxemia and cyanosis
- Croupy cough
- Expiratory wheezing, prolonged expiration, rales and rhonchi
- Tachypnea with apneic episodes
How are children affected by RSV?
Infantile bronchiolitis
Causally related to wheeze and older siblings are spreaders
How are the old affected by RSV?
Major cause of progressive lung disease and winter deaths
How are adults affected by RSV?
Repeated colds, transmitter, very rarely severe
What are treatment options for RSV?
- Vaccines (non)
- Monoclonal antibodies (prophylactically can be used not really therapeutic)
- Anti-virals (prophylactic not really therapeutic)
What is the difference between RSV and influenza?
- Symptoms of influenza and RSV similar in scale, primarily upper respiratory with lower respiratory tract following, influenza a bit more rapid as faster replication.
- To infect human with flue need to select for sero-negativity (those who have not seen that strain of flue) but cannot do the same thing for RSV as all infected by age of 3 and serum type doesn’t change
