RTIs (Pt 2)

Question 1

What age groups are most affected by fatal lower respiratory tract infections ?

Answer 1

• Elderly in developed countries

- Children under five in developing countries

Question 2

Pneumonia:

• Define
• Transmission

Answer 2

PNEUMONIA

• Definition: Inflammation of the substance of the lungs
• Transmission: Access to LRT by inhalation of aerosolised (e.g. sneezing, cough) microbes or by aspiration of normal flora of the URT

Question 3

What is the most common cause of infection-related death in UK and USA ?

Answer 3

Pneumonia

Question 4

Describe the aetiology of pneumonia depending on age.

Answer 4

CHILDREN
• Mainly viral
• Neonates may develop pneumonia caused by Chlamydia trachomatis acquired from mother during birth

ADULTS
• Mainly bacterial
• Aetiology varies with age, underlying disease, occupational and geographic risk factors

Question 5

Identify the main pathogens in viral pneumonia.

Answer 5

Rhinoviruses
Coronaviruses
Influenza virus
Measles virus

Question 6

Identify the main pathogens in bacterial pneumonia.

Answer 6

Streptococcus pneumoniae
Mycobacterium tuberculosis
Haemophilus influenzae
Pseudomonas aeruginosa

Question 7

Define atypical pneumonia. What organisms can cause atypical pneumonia ?

Answer 7

Pneumonia which fails to respond to treatment with penicillin (i.e. “not caused by one of the pathogens most commonly associated with the disease”)

• Mycoplasma pneumoniae
• Legionella pneumophilia
• Chlamydia psittaci
• Chlamydia pneumoniae

Question 8

Identify the main anatomical classifications of pneumonia.

Answer 8

• Lobar pneumonia
• Bronchopneumonia
• Interstitial pneumonia
• Necrotising pneumonia

Question 9

Define lobar pneumonia.

Answer 9

Pneumonia involving a distinct region of the lung ie. lobe.

Question 10

Define bronchopneumonia.

Answer 10

Diffuse, patchy consolidation, associated with bronchi and bronchioles.

Question 11

Define interstitial pneumonia.

Answer 11

Invasion of lung interstitium, usually characteristic of viral infection.

Question 12

Define necrotising pneumonia.

Answer 12

Lung abscesses and destruction of parenchyma

Question 13

Identify the main clinical features of Streptococcus pneumoniae pneumonia.

Answer 13

1) Initially:
- Abrupt onset
- Rigors
- Fever
- Malaise
- Tachycardia
- Dry cough

2) Followed by:
- Productive cough with rusty sputum
- Spiky temperature
- Lobular consolidation

Question 14

Identify the main clinical features of Mycoplasma pneumoniae pneumonia.

Answer 14

• Fever
• Dry cough
• Dyspnoea
• Lymphadenopathy

Question 15

Identify the main clinical features of Haemophilus influenzae pneumonia.

Answer 15

• Mainly occurs in children
• Consolidation or patchy bronchopneumonia
• Persistent purulent sputum and malaise

Question 16

Identify the main clinical features of Legionella pneumophila pneumonia.

Answer 16

=Legionnaire’s disease (form of atypical pneumonia), i.e. severe systemic infection with pneumonia

• Tachypnoea
• Purulent sputum
• Consolidation

Question 17

Legionella pneumophila:

• What type of bacteria ?
• What is its mechanism of action ?
• How is transmitted ?
• Special features ?

Answer 17

• Type of bacteria: Gram negative bacillus
• Mechanism of action: Secretes protease causing lung damage
• Transmission: transmitted by aerosol, but not person-person
• Special feature: usually occurs as outbreaks

Question 18

Describe the laboratory diagnosis of Legionnaire’s Disease.

Answer 18

Detection of antigen in urine (4-fold rise in antibody)

Question 19

What are the main clinical features of Measles ?

Answer 19

• Fever
• Characteristic rash
• Runny nose
• Koplik’s spots

Question 20

What are possible complications of measles ?

Answer 20

→ Neurological complications

→ “Giant cell” (Hecht’s) pneumonia in the immunocompromised – usually fatal

Question 21

Do people usually die from measles ?

Answer 21

In developing countries, yes.

Question 22

MEASLES virus:

• Class of virus
• Transmission
• Where does it replicate ?
• Incubation period
• Is infection localised or sytemic ?

Answer 22

• Class of virus: Paramyxovirus
• Transmission: via aerosol
• Where it replicates: Replicates in LRT
• Incubation period: 10-14 days
• Multisystem infection

Question 23

Describe diagnosis of measles.

Answer 23

• Clinical mainly
• Serology for measles-specific IgM (easiest way)
• Virus isolation
• Viral RNA detection

Question 24

Describe treatment and prevention of measles.

Answer 24

TREATMENT
♣ If severe, ribavarin treatment available
♣ Antibiotics for secondary bacterial infection

PREVENTION
♣ Immunisation with highly effective, live, attenuated MMR vaccine

Question 25

List the main risk factors for pneumonia. Identify the pathogen associated with each risk factor.

Answer 25

- Travel, air conditioning (L. pneumophila) - CF (Pseudomonas) - Bird contact (C. psitacci) - Immigration (M. tuberculosis) - Farming (sheep) (Coxiella burnetti) - Recent influenza (S. pneumoniae, St. aureus)

Question 26

What are the main symptoms, and signs of pneumonia ?

Answer 26

SYMPTOMS - Weakness and malaise - Breathlessness - Cough - Purulent sputum - Chest pain (sharp, due to pleural inflammation) SIGNS - Raised temperature - Purulent sputum - Tachypnoea - Signs of lung consolidation - Cyanosis - Shock

Question 27

How is pneumonia diagnosed ?

Answer 27

- Primarily by history and examination - Radiology can help figure out specific anatomical classification of the pneumonia + rule out other conditions which can mimic pneumonia - Sputum can also be taken (but retrospective, because it takes 48 hours)

Question 28

Define and explain how to calculate a CURB score.

Answer 28

Estimation of mortality of community-acquired pneumonia to help determine inpatient vs. outpatient treatment: 1 point for each feature present: • Confusion of new onset (defined as an AMTS of 8 or less) • Blood Urea nitrogen greater than 7 mmol/l (19 mg/dL) • Respiratory rate of 30 breaths per minute or greater • Blood pressure less than 90 mmHg systolic or diastolic blood pressure 60 mmHg or less • Age 65 or older - If 0 to 1 points, low severity, low mortality, home treatment (1 drug) - If 0 to 1 points, low severity, low mortality but hospital treatment due to reasons other than pneumonia (e.g. social reasons or comorbidity) (1 drug) - If 2 points, moderate severity, moderate mortality, hospital treatment (2 drugs) - If 3-5 points, high severity, high mortality, hospital treatment (and possibly critical care)

Question 29

Distinguish between endemic, epidemic and pandemic disease. Giving an example of disease which causes all three.

Answer 29

- Endemic: Present in a community at all times; at a relatively low to medium frequency but at a steady-state - 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. Influenza causes endemic, epidemic and pandemic disease.

Question 30

INFLUENZA VIRUS - Class of virus - Types - Structure

Answer 30

-Class of virus: Orthomyxovirus -Types: • Type A: epidemics and pandemics, animal reservoir • Type B: epidemics, no animal hosts • Type C: minor respiratory illness -Structure: ♦ Type-specific antigens on cell surface (spikes) (i.e. haemagglutinin (H) and neuraminidase (N)) ♦ Segmented, single stranded RNA. Reassortment gives rise to novel combinations of H and N antigens.

Question 31

Explain the terms antigenic shift and antigenic drift, and explain how they apply to the Influenza virus.

Answer 31

Influenza virus undergoes genetic changes during spread through the host species. 1) Antigenic drift - Small point mutations are constantly occurring in N and H antigens - Allows virus to multiply in individuals with immunity to preceding strains - New sub-type 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. - New virus has novel surface glycoproteins - New strains can infect previously immune populations, and cause pandemic

Question 32

Briefly explain how a pandemic influenza strain can be generated.

Answer 32

"Major changes in the influenza type A HA antigen (antigenic shift) are caused by reassortment from different influenza A subtypes, such as between animal and human subtypes, and in rare events, such shifted viruses can result in strains capable of causing large regional or global pandemic outbreaks"

Question 33

What are the main characteristics of a pandemic ?

Answer 33

- Antigenic shift - Most people have no immunity - Attack rate is high- spreads rapidly - Mortality rate can be high

Question 34

What is the virus of swine flu ? Describe the epidemiology of swine flu. Also describe the attack and mortality rate of swine flu.

Answer 34

-Influenza A virus H1N1 virus -Infection largely limited to individuals under the age of 40 -Attack rate was high but mortality low because many had a degree of immunity because a) Older people had been infected with older H1N1 viruses in childhood b) Vaccine had contained H1N1 components

Question 35

Distinguish between pandemic and seasonal flu.

Answer 35

Seasonal ‘flu – different serotypes Pandemic flu - almost exclusively pandemic H1N1

Question 36

How is influenza diagnosed ?

Answer 36

* Point of care diagnosis (medical diagnosis at or near the point of care) * Nasopharyngeal aspirate * Serum (serology)

Question 37

How is influenza treated and managed ?

Answer 37

TREATMENT • Amantadine • Zanamavir • Oseltamivir (“Tamiflu”) MANAGEMENT - Warmth, rest, hydration, analgesia - Anti-virals within 48 hours has some effect on duration of fever - No antibiotics unless secondary bacterial infection suspected

Question 38

How is influenza prevented ? Describe the main features of this method.

Answer 38

-Killed vaccine (70% efficacy) Trivalent vaccine Antigenic variation means that a new vaccine is required each year New vaccine is based on the PREDICTED strains

Question 39

What groups are particularly critical in the vaccination process of influenza.

Answer 39

Elderly, immunosuppressed and others with respiratory risk (e.g. asthmatics and bronchitics) require an annual vaccine

Question 40

How long does it take to develop a new flu vaccine ? (given that new flu vaccine is required each year)

Answer 40

New recombination methods speed up the process of developing a new vaccine - this was used in the recent swine flu pandemic

Question 41

SARS: - Definition - Symptoms - Incubation period - Transmission - Pathogen

Answer 41

♠ Definition: Outbreak of severe respiratory disease with no identifiable cause ``` ♠ Symptoms: • High fever • Cough • Shortness of breath • CXRs consistent with pneumonia ``` ♠ Incubation period: 2-7 days (10 max) ♠ Transmission: droplets, faeces, infected animals ♠ Pathogen: SARS-associated Coronavirus (SARS CoV)

Question 42

What are the main structural features of SARS coronavirus ? How can SARS coronavirus be identified ?

Answer 42

• Structure: - Enveloped - RNA virus - Characteristic halo - Receptor for spike protein is ACE2 • Identified by: - virus isolation in cell culture - electron microscopy - molecular techniques

Question 43

What is the treatment for SARS ?

Answer 43

• No specific anti-viral treatment available - Ribavirin - Corticosteroids - Interferons - Anti-retroviral therapies (e.g. protease inhibitors) • Whole inactivated virus vaccine and recombinant vaccine now been developed

Question 44

MERS - Pathogen - Symptoms

Answer 44

- Pathogen: MERS-CoV | - Symptoms: Same as SARS

Question 45

What is the leading cause of death globally from a single infectious agent ?

Answer 45

Tuberculosis

Question 46

What are risk factors for TB ?

Answer 46

* AIDS * Increased use of immunosuppressive drugs * Decreased socio-economic conditions * Increased immigration from areas of high endemicity * Multiple drug resistance (MDR) * Overcrowding and poor nutrition

Question 47

What pathogen is responsible for TB ?

Answer 47

Mycobacterium tuberculosis

Question 48

Clinically, what are the main types of TB ? What are the main clinical features of each of these ?

Answer 48

1) Primary TB - Usually asymptomatic - Possible cough and/or wheeze - Possible small transient pleural effusion 2) Miliary TB - Due to 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 (productive cough) - Pleural effusion

Question 49

Mycobacterium tuberculosis: - Type of bacteria - Transmission - Location in body

Answer 49

-Type of bacteria: Neither Gram positive nor Gram negative, obligate anaerobe, human pathogen, acid-fast bacilli -Transmission: Spread by inhalation of organisms from dust / aerosols -Location in body: TB primarily affects lungs (especially well-aerated upper lobes of lungs since obligate aerobe) but can process to other sites (e.g. GI tract)

Question 50

How is TB diagnosed ?

Answer 50

♠ Mantoux test: • Used to detect latent TB infection • Tuberculin injected intradermally • Immune response if individual previously exposed to bacterium (swelling) • Induration (palpable hardened area) measured after 48-72 hours ♠ Specimens (but problem: TB is very slow growing so may have to wait weeks) -Respiratory- sputum, laryngeal, gastric contents, broncho-alveolar lavage, induced sputum -Pus -CSF -Stools Wrt specimens, primary diagnosis is made from visualising acid-fast bacilli in sputum smears. Cultures can also be used.

Question 51

Explain the significance of bacterial load in diagnostics.

Answer 51

1) Patients present at different bacteria loads 2) Diagnostic test become positive at different bacterial loads 3) Reducing bacterial load can delay diagnosis 4) Symptoms differ at different bacterial loads

Question 52

Identify some important diagnostic tools and rank them in order of sensitivity with increased bacterial load.

Answer 52

- Culture most sensitive (can detect even low bacterial load) - PCR intermediate - Smear least sensitive (requires high bacterial load to detect it)

Question 53

Explain how "visualising acid-fast bacilli in sputum smears" works as a way of diagnosing TB.

Answer 53

1) Auramine - Positive organisms fluoresce bright yellow, - More sensitive than Z/N for initial diagnosis because the whole smear can be examined under low power magnification - Tells you about presence or absence 2) Ziehl-Neelsen (Z/N) - High power magnification - Semi-quantification

Question 54

Identify the main ways to culture myobacterium tuberculosis, and explain how culturing can lead to diagnosis.

Answer 54

1) Solid culture: • Lowenstein-Jensen (LJ) slopes: 6 weeks • Middlebrook agar plates: 2-3 weeks 2) Liquid culture: • Mycobacteria Growth Indicator Tube (MGIT): 5-15 days (allows continuous monitoring of positive cultures) 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. NOW, Rapid Automated TB Culture System (Xpert MTB/RIF)

Question 55

Identify the function, pros and cons of Rapid Automated TB Culture System (Xpert MTB/RIF) for TB diagnosis.

Answer 55

♦ Function: Detects TB bacilli + determines RIF resistance ``` ♦ PROS: • A two hour test (quick) • 95% sensitive • 95% specific • Little technical expertise required ``` CONS: • Expensive

Question 56

Describe treatment and prevention for Tuberculosis.

Answer 56

TREATMENT: Prolonged, combination Therapy - isoniazid, rifampicin, ethambutol, pyrazinamide - To prevent emergence of resistance - However, multi-drug resistant TB (MDR-TB) is a major global problem - Minimum of 6 months to eradicate slow growing organisms PREVENTION - Childhood immunisation: live, attenuated, BCG vaccine - Prophylaxis with isoniazid for 1 year ("for the treatment of latent TB infection among people living with HIV and children under five years of age who are contacts of patients with TB")

Question 57

Identify possible fungal infections of the lower respiratory tract.

Answer 57

* Aspergillus fumigatus | * Pneumocystis jiroveci (previously P. carinii)

Question 58

Identify possible infections of the lower respiratory tract.

Answer 58

Viral: Viral pneumonia Measles Influenza (e.g. swine flu, avian flu, SARS, MRES) Bacterial: Bacterial pneumonia TB Fungal: • Aspergillus fumigatus • Pneumocystis jiroveci (previously P. carinii) ``` Parasitic: • Ascaris • Strongyloides • Schistosoma • Echinococcus granulosus ```

Question 59

Identify possible parasitic infections of the lower respiratory tract.

Answer 59

* Ascaris * Strongyloides * Schistosoma * Echinococcus granulosus