Respiratory Infections Flashcards
how do you calculate DALY?
sum of years of life lost (YLL) and years lost to disability (YLD)
what are the signs of an upper respiratory tract infection?
cough
sneezing
runny or stuffy nose
sore throat
headache
what are the signs of a lower respiratory tract infection
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
what are the bacterial causative agents of respiratory infections?
- Streptococcus pneumoniae-most common
- Myxoplasma pneumoniae
- Haemophilus Influenzae
- Mycobacterium tuberculosis- highest annual mortality
what are the viral causative agents of respiratory infections?
- Influenza A or B virus
- Respiratory Syncytial Virus
- Human metapneumovirus
- Human rhinovirus- most commonly identified pathogen in individual with respiratory illness
- Coronavirus
what are the demographic and lifestyle factors increasing risk for pneumonia?
age <2 or >65 years
cigarette smoking
excess alcohol consumption
what are the social factors for increased risk pneumonia?
contact with children <5
poverty
overcrouding
what are the medications that increase the risk of pneumonia?
inhaled corticosteroids
immunosuppressants
PPIs
what medical history can increase risk for pneumonia?
COPD, asthma
heart disease
liver disease
diabetes mellitus
HIV, malignancy, hyposplenism
complement or Ig deficiencies
risk factors for aspiration
previous pneumonia
what specific risk factors can increase risk for certain pathogens?
geographical variations
animal contact
healthcare contacts
by what overall groups can bacterial infections be acquired?
community-acquired pneumonia
hospital-acquired pneumonia
ventilator acquired pneumonia
what are the features of a common/ typical bacteria?
gram +ve
extracellular
opportunistic
(easier to culture and identify)
what are some examples of typical bacteria?
streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
what are the features of atypical bacteria?
slower growing
intracellular or extracellular
gram +ve or gram -ve
what are some examples of CAP?
- Streptococcus pneumoniae (40-50%)
- Myxoplasma pneumoniae
- Staphylococcus aureus
- Chlamydia pneumoniae
- Haemophilus Influenzae
what are some examples of hospital acquired pneumonia?
- Staphylococcus aureus
- Psuedomonas aeruginosa
- Klebsiella species
- E. Coli
- Acinetobacter spp.
- Enterobacter spp.
why is HAP harder to treat?
usually more drug resistance so require higher number of antibiotics
what are some examples of VAP?
- Psuedomonas aeruginosa (25%)
- Staphylococcus aureus(20%)
- Enterobacter
what are some examples of atypical bacteria?
myxoplasma pneumonia
chlamydia pneumonia
legionella pneumophilia
what is the mechanisms of actions of acute bacterial pneumonia?
what are the overall treatments for bacterial pneumonia?
- supportive treatment
- antibiotics
what supportive treatment is given in bacterial pneumonia?
- Oxygen (hypoxia)
- Fluids (dehydration)
- Analgesia (pain)
- Nebulised saline (may help expectoration)
- Chest physiotherapy?
what antibiotics are given in bacterial pneumonia?
penicillins (amoxicillin)
macrolides (clarithromycin)
how do penicillins work?
- Beta-lactams that bind proteins in the bacterial cell wall to prevent transpeptidation
- Only effective against gram +ve bacteria (usually typical bacteria)
how do macrolides work?
Bind to bacterial ribosome to prevent protein synthesis
what determines what drug is given for bacterial pneumonia?
CURB-65 score (score of severity of pneumonia)
CAP or HAP
what antibiotic is given in CAP/HAP?
what is key to increasing the success of antibiotics?
- Time to administration (for every hour in septic shock- survival reduced by 7.9%)
- Using an effective antibiotics- typical CAPS may respond to penicillin’s, atypical CAPs require macrolides
how do sulphonamides work?
inhibit folate synthesis
what is a microbiota?
ecological community of microbes found inside multi-cellular organism
present in healthy individuals
in oropharynx
- Haemophilus influenza
- Staph. Aureus
- Strep. Pneumoniae – rarely caught
In nose
- Strep. Pneumoniae
what is commensural bacteria?
microbes that live in a ‘symbiotic’ relationship with their host. Providing vital nutrients to the hose in the presence of a suitable ecological niche
what is an oppourtunistic pathogen?
microbe that takes advantage of a change in condition (often immuno-suppression)
what is a pathobiont?
a microbe that is normal commensal but if found in the wrong environment (e.g anatomical site) can cause disease
what are the risk factors of mycobacterium tuberculosis?
HIV
Alcohol
smoking
geographical and socioeconomic status
how does TB cause disease?
what is the treatment for mycobacterium tuberculosis?
- Latent is highly resistant to immune system
- Standard treatment requires a combination of 4 antibiotics for a 6-month period
- Multidrug resistant TB (commonly rifampicin) increasing
what antibiotics are used for mycobacterium tuberculosis and where do they act?
- isoniazad
- ethambutol
- pyrazinamide
- rifampin
can you have a commensal respiratory virus?
NO
how are viral infections differentiated
by serotypes
virus which cannot be recognised by serum (antibodies) that recognise another- implication for protective immunity
distinguished by common antigens
what is the most common viral infection?
rhinovirus
what are the effects of viral infection on the body?
what receptors does rhinovirus bind to?
ICAM-1
minor group low density lipoproteins
what does H1N1 influenza A bind to?
haemogglutinin binds alpha2, 6 sialic acids largely in upper respiratory tract
what does H5N1 avian flu bind to?
haemogglutinin binds alpa2, 3 sialic acids in lower respiratory tract
what does respiratory syncytial virus bind to?
F and G proteins bind glycosaminoglycans in receptors like IGFR1 and nucleolin
throughout all respiratory tract
what does SARS-CoV-2 bind to?
Spike (S) protein binds ACE2
largely in nasal epithelium and type 2 pneumocytes in lungs
why are smokers more affected by SARS-CoV-2?
increased expression of S protein in nasal epithelium and type 2 pneumocytes
what are the factors of influenza?
no-reinfection by same strain
imperfect vaccines
what are imperfect vaccines in influenza?
vaccine-induced immunity rapidly wanes
mainly homotypic immunity
annual vaccination required
can RSV-2 serotypes (A and B) cause re-infection?
yes
recurrent re-infection with similar strains
what is the vaccine status for RSV-2?
no vaccine
poor immunogenicity
vaccine-enhanced disease
what disease can RSV cause in infants?
bronchiolitis
(leading cause of infant hospitalisation in developed world)
what proportion of patients get RSV?
all children infected by age of 3
50% by age of 1
what are the risk factors for bronchiolitis?
premature birth
congenital heart and lung disease
what are the signs and symptoms of bronchiolotis?
- Nasal flaring
- Chest wall retraction
- Hypoxaemia and cyanosis
- Croupy cough
- Expiratory wheezing, prolonged expiration, rales and rhonchi
- Tachypnea with apenic episodes
what is the risk of RSV in older generation?
also high risk in older individuals
similar deaths to that of flu
what is the age dependant trends of RSV?
- age dependence of RSV
- young children
- infantile bronchiolitis
- causally related to wheeze
- older siblings are spreaders
- caring adults
- repeated colds
- transmitters
- very rarely severe
- old and infirm
- major cause of progressive lung disease and winter deaths
- young children
what viruses are similar to RSV at lower prevalence?
hMPV
PIV
what are the treatment options for RSV?
- support- oxygen
- preventative and therapeutic- no vaccines
- prophylactically- monoclonal antibodies and antivirals
what is the difference between influenza and RSV?
- flu
- has a greater viral load= faster replication
- pre-selected for seronegative- levels require no previous infection
- RSV
- Antibodies diminish rapidly after infection so not pre-selected for seronegativity- previous infection NOT limiting (also seen in coronaviruses)
- Slower viral load- slower replication
what is the interplay between viral and bacterial infections?
coinfections and superinfections common
- Virus may lay ground word and then death caused by a bacterial infection
- There is also an interplay with chronic lung disease- higher viral bacterial load with lung diseases
what factors can cause severe disease?
- Highly pathogenic strains (zoonotic)
- Absence of prior immunity
- Innate immunodeficiency (gene variant IFITM3)
- B cells (antibody-presumably local)
- T cells (correlate with peripheral levels)
- Predisposing illness/ conditions
- Frail elderly
- COPD/ asthma
- Diabetes, obesity, pregnancy etc
what is a zoonotic diesase?
disease passed from a non-human animal to human
how do interferons (IFN) work in host defence?
- Directly produced by infected cells or immune cells
- Named for ability to interfere with viral infection in vitro
- Family of cytokines
- Produce interferon stimulated genes that have the ability to directly inhibit viral replication
- 3 groups
- Type 1 (IFN alpha/ IFN betas)
- Type 2 (IFN-gamma)
- Type 3 (IFN- lambda)
what is long term immunity provided by?
B-cells
why did the H1N1 pandemic affect the young generation?
pre-existing immunity limited disease in over 60s
what is the first immune cell recruited in host defence?
neutrophile
what immune response is generated in prolonged pneumonia?
adaptive immune response
macrophage, T cell, monocyte
