10-11-22 – Respiratory Tract Infections 1 Flashcards
Learning outcome
- Describe the normal host defense mechanisms of the respiratory tract and how these influence infection
- Describe the ways in which pathogens establish infections in the respiratory tract
- Detail the infective agents which cause respiratory tract infections
- Recognise and describe the clinical features of respiratory tract infections
- Define how to make a diagnosis of respiratory tract infections
- Identify the main treatment modalities for respiratory tract infections
- Outline ways of reducing the burden of respiratory tract infections
- Understand the nature of and pathogenesis of influenza virus, and the threat of a new pandemic….COVID-19
- Explain how the different forms of tuberculosis occur
Respiratory tract infection locations diagram
Overview of RTIs
- Overview of RTIs:
1) Common cold
2) Otitis & Sinusitis
3) Oral Cavity infections
4) Pharyngitis & Tonsillitis
5) Parotitis
6) Epiglottitis
7) Diphtheria
8) Laryngitis & Tracheitis
9) Whooping Cough
10) Bronchitis
11) Bronchiolitis
12) Pneumonia
13) Influenza
14) SARS
15) TB
16) (Fungal Infections)
17) (Parasitic Infections)
What are 4 common organisms in RT (respiratory tract) microbiota?
What are 3 occasional organisms in RT microbiota?
What are 4 conditions that are latent in tissues?
- 4 common organisms in respiratory tract (RT) microbiota (>50% of people):
1) Bacteroides spp.
2) Candida albicans
3) Oral Streptococci
4) Haemophilus influenzae
- 4 occasional organisms in RT microbiota (<10% normal people)
1) Streptococcus pyogenes
2) Streptococcus pneumoniae
3) Neisseria meningitidis
- 4 latent (dormant) viruses in tissues
1) Herpes simplex virus type I (HSV)
2) Epstein-Barr virus (EBV)
3) Cytomegalovirus (CMV)
4) Mycobacterium tuberculosis
What are 6 parts of RT host defences?
- 6 parts of RT host defences:
1) Saliva
2) Mucus
3) Cilia (muco-ciliary escalator/elevator)
4) Nasal secretions
5) Antimicrobial peptides
6) Alveolar macrophages
What is another name for the common cold?
How is it transmitted?
What are 5 causative agents of the common cold?
What time of the year does the common cold appear?
Describe the pathogenesis of the common cold (in picture)
- The common cold is known acute coryza
- It can be transmitted via aerosol and virus-contaminated hands
- 5 causative agents of the common cold:
1) 40% Rhinoviruses (>100 serotypes)
2) 30% Coronaviruses (>3 serotypes)
3) Coxsackie virus A
4) Echovirus
5) Parainfluenza virus
- With there being differences in pathology and epidemiology of each causative agent
- The common cold is seasonal, with it appearing in early autumn and mid / late spring
What are 7 clinical features of the common cold?
Is it self-limiting? Is there a vaccine?
- 7 clinical features of the common cold:
1) Tiredness
2) Slight pyrexia
3) Malaise
4) Sore nose & pharynx
5) Profuse, watery nasal discharge becoming mucopurulent
6) Sneezing in early stages
7) Secondary bacterial infection occurs in minority
- The common cold is generally mild and self-limiting
- There is no vaccine
What are 6 virus causative agents for Acute Pharyngitis & Tonsillitis?
What are 3 bacterial causative agents for Acute Pharyngitis & Tonsillitis?
- 6 virus causative agents for Acute Pharyngitis & Tonsillitis:
1) Epstein-Barr virus (EBV)
2) Cytomegalovirus (CMV)
3) Herpes simplex virus type I (HSV-1)
4) Rhinovirus
5) Coronavirus
6) Adenovirus
- 3 bacterial causative agents for Acute Pharyngitis & Tonsillitis:
1) Streptococcus pyogenes
2) Haemophilus influenzae
3) Corynebacterium diphtheriae
How does Cytomegalovirus (CMV) transmit?
Is it symptomatic?
When can it reactivate?
How can be diagnose a CMV infection?
How can we diagnose CMV pneumonitis?
What 3 things do we treat CMV with?
- Transmission of CMV is in body secretions and organ transplants
- CMV is usually asymptomatic or mild in healthy adults
- CMV can reactivate and cause disease when cell-mediated immunity is compromised (e.g HIV/AIDS)
- To diagnose 2° CMV infection, we use IgM in blood
- To diagnose CMV pneumonitis, there is CMV Antigens present in BAL (Bronchoalveolar lavage – fluid sample taken during bronchoscopy)
- 3 things we treat CMV with:
1) Ganciclovir
2) Foscarnet
3) Cidofovir
Where does Epstein-Barr Virus (EBV) replicate?
What does it cause?
What 2 ways is it transmitted?
What are the 2 peaks EBV usually occurs in?
How long is EBV incubation? How long is EBV illness?
- Epstein-Barr Virus (EBV) replicates specifically in B lymphocytes (CD21 receptor)
- EBV causes glandular fever
- It is transmitted by saliva and aerosol
- EBV usually occurs in 2 peaks:
1) 1-6 years old
2) 14-20 years old
- EVC incubation is 4-8 weeks
- EVC illness usually lasts 4 – 14 days
What are 12 clinical features of glandular fever?
- 12 clinical features of glandular fever:
1) Fever
2) Headache
3) Malaise
4) Sore throat
5) Anorexia
6) Palatal petechiae
7) Cervical lymphadenopathy
8) Splenomegaly
9) Mild hepatitis
10) Swollen tonsils and uvula
11) Petechiae on the soft palate
12) White exudate
What are 3 ways we can detect heterophile antibodies (IgM) specific for EBV?
What is the treatment for glandular fever?
What are 3 complications of Glandular fever?
- 3 ways we can detect heterophile antibodies (IgM) specific for EBV:
1) Monospot test
2) Paul-Bunnell test
3) If negative – consider HIV conversion
- Glandular fever should not be treated with antibiotics (ampicillin & amoxycillin)
- Contact sports or heavy lifting should be avoided during the first month of illness and until any splenomegaly has resolved
- 3 complications of Glandular fever:
1) Burkitt’s lymphoma
2) Nasopharyngeal carcinoma
3) Guillain-Barré syndrome
What is tonsilitis caused by?
What 2 ways does it transmit?
What group does infection mainly occur in?
What % of people are asymptomatic carriers?
What treatment is it susceptible to?
What 2 things is it becoming more resistant to?
What are 4 clinical features of tonsilitis?
- Tonsilitis is caused by Streptococcus pyogenes
- Transmission occurs by airborne droplets and contact
- Infection occurs mainly in children
- 15-20% become asymptomatic carriers
- Tonsilitis is susceptible to treatment with penicillin
- It has Increasing resistance to erythromycin and tetracycline
- 4 clinical features of tonsilitis:
1) Fever
2) Pain in throat
3) Enlargement of tonsils
4) Tonsillar lymphadenopathy
What kind of streptococcus is Streptococcus pyogenes? Is it gram positive or negative?
How is it cultured? What kind of activity does it display?
How can it be treated?
What are 5 complications of Streptococcus pyogenes?
- Streptococcus pyogenes is a Group A Streptococcus
- It is a gram-positive cocci in chains
- It can be cultured on blood agar
- Streptococcus pyogenes displays haemolytic activity due to exotoxin streptolysin
- It is susceptible to treatment with penicillin
- 5 complications of Streptococcus pyogenes:
1) Scarlet Fever – Caused by erythrogenic toxin from S. pyogenes
2) Peritonsillar abscess (“quinsy”)
3) Otitis media / sinusitis
4) Rheumatic heart disease
5) Glomerulonephritis
What is parotitis caused by?
What group of people does it primarily affect?
What family is this virus caused by?
What 2 ways does it transmit?
How long until onset of disease?
How does diagnosis occur?
What are 6 different clinical features of parotitis?
What are 3 different parts of the treatment of parotitis?
How can it be prevented?
What are 2 potential complications from parotitis?
- Parotitis is caused by the mumps virus, which is from the paramyxovirus family
- It primarily affects school-aged children and young adults
- Transmission occurs by droplet spread and fomites (objects/materials)
- This virus is contracted 2 days before disease onset
- Diagnosis of parotitis is based on clinical features - IgM serology can be performed in doubtful cases from saliva, CSF or urine
- 6 different clinical features of parotitis:
1) Fever
2) Malaise
3) Headache
4) Anorexia
5) Trismus - restriction of the range of motion of the jaws
6) Severe pain and swelling of parotid gland(s)
- 3 different parts of the treatment of parotitis:
1) Mouth care
2) Nutritional
3) Analgesia
- Parotitis can be prevented through immunisation (MMR vaccine)
- 2 potential complications from parotitis:
1) CNS involvement
2) Epididymo-orchitis (~30% infected after puberty)
* Epididymo-orchitis is an inflammation of the epididymis and/or testicle (testis)
* Epididymitis is where a tube (the epididymis) at the back of the testicles becomes swollen and painful
What is acute epiglottitis caused by?
Where is it seen most often?
How is it prevented?
What are 4 clinical features of acute epiglottitis?
How do we diagnose acute epiglottitis?
What are 2 parts of the treatment of acute epiglottitis?
- Acute epiglottitis is caused by Haemophilus influenzae and is a life-threatening emergency
- It is most often seen in young children
- Acute epiglottitis has been prevented by the Hib vaccine (Haemophilus influenzae type b)
- 4 clinical features of acute epiglottitis:
1) High fever
2) Massive oedema of the epiglottis
3) Severe airflow obstruction resulting in breathing difficulties
4) Bacteraemia
- To diagnose, we do not examine throat or take throat swabs as this will precipitate complete obstruction of airway
- We use blood cultures to isolate H. influenzae
- 2 parts of the treatment of acute epiglottitis:
1) Requires urgent endotracheal intubation
2) Intravenous antibiotics (ceftriaxone or chloramphenicol)
What family is Haemophilus influenzae from?
What type of bacteria is it?
What resistance do they some clinical strains have?
Where is it present in most healthy people?
How is the Haemophilus influenzae in the Hib vaccine modified?
- Haemophilus influenzae is part of the Pasteurellaceae family
- It is a gram-negative bacillus
- Some clinical strains have β-lactamase and may be resistant to ampicillin
- Haemophilus influenzae is present in nasopharynx of 75% healthy people
- the Haemophilus influenzae in the Hib vaccine is modified and has a polysaccharide capsule
Where is diphtheria present?
What groups of people does it affect?
What bacteria causes diphtheria?
Where is it present in some healthy people?
What are 5 clinical features of diphtheria?
How do we diagnose diphtheria?
What are 3 parts of the treatment of diphtheria?
How do we prevent diphtheria?
- Diphtheria is rare in developed countries as a result of vacation
- It is usually a childhood disease, but may affect adults in countries where childhood vaccination uptake is poor
- Diphtheria is caused by Corynebacterium diphtheriae
- It is present in 3-5% of healthy throats
- The incubation period for diphtheria is 2-7 days
- 5 clinical features of diphtheria:
1) Sore throat
2) Fever
3) Formation of pseudomembrane
4) Lymphadenopathy
5) Oedema of anterior cervical tissue (bull-neck)
- Diphtheria diagnosis is made on clinical grounds as therapy is usually urgently required
- 3 parts of the treatment of diphtheria:
1) Prompt anti-toxin therapy administered intramuscularly
2) Concurrent antibiotics (penicillin or erythromycin)
3) Strict isolation
* Prevention of diphtheria is through childhood immunisation with toxoid vaccine
* Booster doses given if individual is travelling to endemic areas if its been >10 years have elapsed since primary vaccination
What is Corynebacterium diphtheriae?
What do only toxin-producing strains cause?
What are the 2 subunit toxins?
How is it transmitted?
What 4 places does it colonise?
- Corynebacterium diphtheriae is a human pathogen
- Only toxin-producing strains cause disease
- 2 subunit toxins:
1) Subunit A (Active): responsible for clinical toxicity
2) Subunit B (Binding): transports toxin to receptors on myocardial and peripheral nerve cells
- Corynebacterium diphtheriae is transmitted through air-borne droplets
- 4 places Corynebacterium diphtheriae colonises:
1) Pharynx
2) Larynx
3) Nose
4) (Rarely skin and genital tract)
How can laryngitis and tracheitis be caused?
How does it usually originate?
What are 4 different viral causes?
How does it present differently in adults and children?
- Laryngitis and tracheitis can be caused by infections spreading down from the upper respiratory tract
- Laryngitis and tracheitis are usually viral in origin
- 4 different viral causes:
1) Parainfluenza virus
2) Respiratory Syncytial virus
3) Influenza virus
4) Adenovirus
- In adults, it presents with hoarseness and retrosternal pain
- In children, it presents with dry cough and inspiratory stridor (croup)
- Stridor is noisy breathing that occurs due to obstructed air flow through a narrowed airway
What organism causes whooping cough?
Who is whooping cough most common in?
How many cases and deaths occur annually?
How common is it in developed counties?
How is it transmitted?
What is its incubation period?
What are the 2 stages of whooping cough?
What are 3 ways whooping cough is diagnosed?
What are 4 different parts of treatment of whooping cough?
How can whooping cough be prevented?
- Whooping cough (aka pertussis) is caused by the bacteria Bordetella pertussis
- For whooping cough, 90% cases in children
- There are >50 million cases worldwide annually and 600,000 deaths worldwide annually
- It is uncommon in developed countries
- Whooping cough is transmitted via air-borne droplets
- The incubation period is 1 – 3 weeks
- 2 stages of whooping cough:
1) Catarrhal stage (1 week)
* Highly contagious
* Malaise
* Mucoid rhinorrhoea
* Conjunctivitis
2) Paroxysmal stage (1-4 weeks)
* Paroxysms (outbursts) of coughing with a classic inspiratory “whoop”
* Lumen of respiratory tract is compromised by mucus secretion and mucosal oedema
- ways whooping cough is diagnosed:
1) Clinically by characteristic “whoop”
2) Bacterial isolation from nasopharyngeal swabs
3) NAAT (nucleic acid amplification test)
- 4 different parts of treatment of whooping cough:
1) In catarrhal stage can be treated with erythromycin
2) In paroxysmal stage, antibiotics have no effect
3) Isolation
4) Supportive care (hospitalisation for infants)
- Whooping cough can be prevented by vaccination (whole cell vaccine)
What type of bacteria is Bordetella pertussis?
What type of pathogen is it?
Where does it replicate?
How does specific attachment occur?
What are the 4 toxic factors of Bordetella pertussis?
- Bordetella pertussis is a Gram-negative aerobic coccobacillus
- It is a human pathogen
- It attaches to and replicates in the ciliated respiratory epithelium, but does not invade deeper structures
- Specific attachment is due to surface components eg. filamentous haemagglutinin (FHA)
- toxic factors of Bordetella pertussis:
1) Pertussis toxin (Ptx)
2) Adenylate cyclase toxin
3) Tracheal cytotoxin
4) Endotoxin
What is incidence?
Whooping cough incidence?
When was the whole heat-killed vaccine for whooping cough introduced?
When do epidemics occur?
- Incidence refers to the number of individuals who develop a specific disease or experience a specific health-related event during a particular time period
- Whooping cough incidence:
- The whole heat-killed vaccine for whooping cough introduced in 1958
- Epidemics occur at approximately 4-year intervals
- Concern over vaccine side effects led to reduced vaccine uptake (~30%) and large epidemic in 1978-9
What is measles caused by?
What is it one of the leading causes of?
What are 4 clinical features of measles?
What 2 things can measles result in?
What 3 ways can we diagnose measles?
What is the treatment for measles?
How do we prevent measles?
- Measles is caused by the measles virus
- Measles is one of the leading causes of death among children globally
- 4 clinical features of measles:
1) Fever
2) Runny nose
3) Koplik spots
4) Characteristic rash
- 2 things can measles result in:
1) May result in neurological complications
2) Can cause “giant cell” (Hecht’s) pneumonia in the immunocompromised – usually fatal
- 3 ways can we diagnose measles:
1) Serology for measles-specific IgM
2) Virus isolation
3) Viral RNA detection
- If severe, measles are treated with ribavirin, and antibiotics for secondary bacterial infections
- To prevent measles, we use immunisation through highly effective, live, attenuated MMR vaccine
What type of virus is the influenza virus?
What are the 3 types of influenza virus?
What do each of them cause?
What are the 2 type-specific antigens on the cell surface (spikes) oof influenza?
What type of genetic material does influenzas have?
What does reassortment of this genetic material lead to?
- 3 types of influenza virus:
1) Type A
* Causes epidemics & pandemics
* Animal reservoir
* Epidemic - Sudden severe outbreak within a region or a group
* Pandemic - Occurs when an epidemic becomes widespread and affects a whole region, a continent, or the entire world
2) Type B
* Causes epidemics
* No animal hosts
3) Type C
* Minor respiratory illness
- 2 type-specific antigens on the cell surface (spikes) of influenza:
1) Haemagglutinin (H)
2) Neuraminidase (N)
- Influenza has single stranded segmented RNA
- Reassortment (“shuffling”) gives rise to novel (new) combinations of H and N antigens
When does the influenza virus go through genetic changes?
How does it do this? What is antigenic drift and shift?
What can each of them lead to?
- The influenza virus undergoes genetic changes during spread through the host species
- It does this through antigenic drift and antigenic shift
1) Antigenic drift
* Small point mutations in the H and N antigens occurs constantly
* Allows the virus to multiply in individuals with immunity to preceding strains
* New subtype can re-infect community
* Occurs with all influenza types
2) Antigenic shift
* Sudden major change based on recombination between two different virus strains when they infect the same cell
* Produces a virus with novel surface glycoproteins
* New strain can spread through previously immune populations – new pandemic
What is swine flu?
What did the vaccine contain?
Who was infection mostly limited to?
What were attack rate and mortality rate like?
- Swine flu is swine influenza (H1N1 virus)
- The vaccine contained H1N1 components
- Infection was largely limited to individuals under the age of 40
- The attack rate was high but mortality low because many had a degree of immunity
What is SARS -CoV?
What 3 ways is it identified?
What is the structure of SARS-Cov 2 like?
What is the receptor for its spike protein?
- SARS-Cov is severe acute respiratory syndrome associated coronavirus
- Infection with SARS-CoV2 causes coronavirus (Covid-19)
- 3 ways SARS-CoV2 is identified:
1) Virus isolation in cell culture
2) Electron microscopy
3) Molecular techniques
- The structure of SARS-CoV2 Is an enveloped RNA virus with a characteristic halo
- The receptor for its spike protein is ACE2
What are the 3 stages in the pathogenesis of SARS-COV2?
- 3 stages in the pathogenesis of SARS-COV2:
1) Stage 1
* Asymptomatic state (1-2 of infection)
2) Stage 2
* Upper airway and conducting airway response (next few days)
3) Stage 3
* Hypoxia, ground glass infiltrates & progression to ARDS
What is tuberculosis caused by?
What is it the second leading cause of?
What 6 things are associated with TB?
What are 3 different types of TB?
What are 3 clinical features of Primary TB?
What are the 2 clinical features of Miliary TB?
What are 6 clinical features of Post-primary TB?
- Tuberculosis is caused by Mycobacterium tuberculosis
- Tuberculosis is the 2nd leading cause of death globally from a single infectious agent
- 6 things associated with TB:
1) AIDS
2) Increased use of immunosuppressive drugs
3) Decreased socio-economic conditions
4) Increased immigration from areas of high endemicity
5) Multiple drug resistance (MDR)
6) Overcrowding and poor nutrition
- 3 different types of TB:
1) Primary TB
* Usually symptomless
* May be associated with cough and wheeze
* Small transient pleural effusion may occur
2) Miliary TB
* Results from acute diffuse dissemination of bacillus
* Fatal without treatment
3) Post-primary TB
* Onset of symptoms over weeks / months
* Malaise
* Fever
* Weight loss
* Mucoid, purulent or blood-stained sputum
* Pleural effusion
What is the Mantoux test used for?
What are the 3 steps to the Mantoux test?
What test did it replace?
- The Mantoux test is used to detect latent TB infection
- 3 steps to the Mantoux test:
1) Tuberculin injected intradermally
2) Immune response if individual previously exposed to bacterium
3) Induration (palpable hardened area) measured after 48-72 hours
- The Mantoux test replaced the Heaf test in UK in 2005
What type of bacteria is Mycobacterium tuberculosis?
What is acid-fastness?
What type of pathogen is Mycobacterium tuberculosis?
Where is it found in the respiratory tract?
Why is this?
How is it spread?
Where do it primarily cause disease?
- Mycobacterium tuberculosis is neither Gram positive nor negative
- It is an acid-fast bacilli
- Acid-fastness is a physical property of certain bacterial and eukaryotic cells, as well as some sub-cellular structures, specifically their resistance to decolorization by acids during laboratory staining procedures
- Mycobacterium tuberculosis is a human pathogen
- It is found in well-aerated upper lobes of lungs, as it an obligate aerobe, meaning it needs oxygen to grow
- Mycobacterium tuberculosis is spread by inhalation of organisms from dust / aerosols
- It primarily causes disease of the lungs, but may proceed to other sites e.g. GI tract
What are the 4 different effects of bacterial load on treatment?
- 4 different effects of bacterial load on treatment:
1) Symptoms differ at different bacterial loads
2) Patients present at different bacterial loads
3) Diagnostic tests become positive at different bacterial loads
4) Reducing the bacterial load can delay the diagnosis
How is a primary diagnosis of TB made?
What are 2 ways this can be done in microscopy?
What are 2 ways this can be done in microscopy?
- Primary disease diagnosis of TB is made from visualising acid-fast bacilli in sputum smears
- 2 ways this can be done in microscopy:
1) Auramine stain
* Positive organisms fluoresce bright yellow,
* More sensitive than Z/N for initial diagnosis because the whole smear can be examined under low power magnification
* Presence or absence
1) Ziehl-Neelsen (Z/N) stain
* Carbol fuchsin stain and methylene blue counter stain.
* 100 fields examined under 100x objective
* Semi-quantification
What are 3 different culture methods for TB?
How long does each method take?
How is bacterial growth measured? How is this done?
- 3 different culture methods for TB:
1) Lowenstein-Jensen (LJ) slopes
* Solid culture
* 6 weeks
2) Middlebrook agar plates
* Solid culture
* 2-3 weeks
3) Mycobacteria Growth Indicator Tube (MGIT)
* Liquid culture
* 5-15 days
- Bacterial growth is measured by the consumption of oxygen in the media.
- Tubes contain a fluorescence compound sensitive to the presence of oxygen.
- Actively respiring bacteria consume oxygen from the media allowing fluorescence to be detected.
What are 6 advantages of the Xpert MTB/RIF: Rapid Automated TB Culture System?
What is a disadvantage?
- 6 advantages of the Xpert MTB/RIF: Rapid Automated TB Culture System:
1) A two-hour test
2) Detects TB bacilli
3) Determines RIF resistance
4) 95% sensitive
5) 95% specific
6) Little technical expertise
- A disadvantage is that it is expensive
