Respiratory > Tuberculosis > Flashcards

Tuberculosis Flashcards

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1
Q

What is TB primarily caused be?

A

The bacterium Mycobacterium tuberculosis

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2
Q

What organs does it affect?

A

Mainly the lungs
Can involve other organs

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3
Q

What do we call TB that mainly affects the lungs?

A

Pulmonary TB

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4
Q

What do we call TB that can also affect other organs?

A

Extrapulmonary TB

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5
Q

What are the social factors for mortality due to TB?

A

Poverty
Low income
Social exclusion
Barriers to healthcare
Overcrowding living conditions
Poor ventilation
Country of birth

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6
Q

What are other factors for mortality due to TB?

A

Advanced age
HIV co-infection
Comorbidities - diabetes, chronic kidney disease, malnutrition
Substance misuse
Mental health conditions

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7
Q

What are the key features of the structure of mycobacterium tuberculosis?

A

Cell wall
Acid-fastness
Capsule
Intracellular lifestyle adaptations
Slow growth

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8
Q

Describe the cell wall feature

A

Unique, complex and waxy cell wall rich in mycolic acids (long chain fatty acids)
Lipid-rich wall - hydrophobic nature
Resistant to many disinfectants and antibiotics

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9
Q

What does the cell wall consist of?

A

Peptidoglycan layer
Arabinogalactan layer
Lipoarabinomannan (LAM)
Mycolic acids

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10
Q

Describe the peptidoglycan layer

A

Rigid mesh-like polymer
Provides structural integrity
Consists of sugars and amino acids

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11
Q

Describe the arabinogalactan layer

A

polysaccharide layer covalently linked to peptidoglycan
Acts as a scaffold for attaching mycolic acids

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12
Q

Describe the lipoarabinomanna (LAM)

A

Complex glycolipid embedded in the outer membrane
Modulates host immune response by interfering with macrophage activation and cytokine production

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13
Q

Describe the acid-fastness feature

A

Waxy cell wall prevents conventional staining
Requires acid-fast staining
Key diagnostic feature

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14
Q

Describe the capsule feature

A

Slimy, polysaccharide-rich capsule layer surrounding the cell
Helps immune evasion

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15
Q

Describe the intracellular lifestyle adaptations feature

A

Able to survive and replicate inside macrophages by resisting phagosome-lysosome fusion

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16
Q

Describe the slow growth feature

A

Complex cell wall and metabolic characteristics contribute to a slow doubling time, making TB culture slow (weeks)

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17
Q

Describe latent TB

A

Occurs when a person inhalers mycobacterium tuberculosis bacilli and the immune system contains the infection
Bacteria remain alive but dormant inside granulomas (normally in the lungs)
No symptoms
Non-infectious
5-10% lifetime risk of progressing to active TB
Risk higher is immune system weakens eg HIV, diabetes, immunosuppressed

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18
Q

Describe active TB

A

Occurs when the immune system fails to contain the bacteria or latent bacteria reactivate
Bacteria multiply actively, causing tissue damage and clinical disease
If pulmonary or laryngeal TB, can spread to others through airborne droplets

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19
Q

What are the intrinsic factors that contribute to resistance?

A

Thick, lipid-rich cell wall
Efflux pumps
Slow growth rate and dormancy

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20
Q

How does the thick, lipid-rich cell wall lead to resistance?

A

Acts as a barrier to many antibiotics as permeability is reduced

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21
Q

How do efflux pumps contribute resistance?

A

Actively expels drugs out of the cell, lowering intracellular drug concentrations

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22
Q

How does slow growth rate and dormancy contribute resistance?

A

Reduced drug susceptibility as many first-line TB drugs target actively dividing cells
When slow-growing/dormant, processes are minimally active so drugs are less effective

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23
Q

What are the extrinsic factors that contribute to resistance?

A

Poor adherence to treatment
Inadequate treatment regimens (suboptimal combinations, incorrect doses or resistant antibiotics as per susceptibility testing)
Interrupted drug supply or stock shortages
Delayed diagnosis and initiation of therapy
Previous TB treatment

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24
Q

What are the virulence factors?

A

Lipoarabinomannan within cell wall
Type VII secretion system
Iron acquisition systems

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25
Describe the lipoarabinomannan within cell wall virulence factor
Inhibits T-cell proliferation Interferes with host immune signalling Helps TB survive within macrophages
26
What is T-cell proliferation?
The process where a T lymphocyte (T-cell) divides to create more T cells
27
Describe the type VII secretion system (ESX-1) virulence factor
Using ESX-1, it inhibits phagosome-lysosome fusion, allowing bacteria to survive and replicate intracellularly Infected macrophages release cytokines like TBF-alpha and IL-12. Cytokines recruit additional immune cells to site of infection Formation of granulomas, a hallmark of TB
28
Describe the iron acquisition systems virulence factor
Produces siderophores(mycobactin)to scavenge iron Iron is crucial for growth and survival in host cells Allows TB to survive and replicate inside iron-limited environments like macrophage phagosomes
29
What are siderophores?
Small, iron-chelating molecules produced by microorganisms like bacteria and fungi to scavenge iron from the environment
30
What is the primary source of mycobacterium tuberculosis?
Humans
31
How is TB transmitted?
Primarily human to human Via airborne droplets
32
When does transmission happen?
When an infected person with pulmonary or laryngeal TB coughs, sneezes or speaks - expels infectious droplets
33
What is mycobacterium bovis?
Found in cattle Can infect humans via unpasteurised milk or close contact
34
Which type of TB is the most common?
Pulmonary TB
35
TB symptoms
Chronic cough - productive and sometimes with haemoptysis Fever Night sweats Weight loss Pleuritic chest pain Breathlessness
36
Which patients does extrapulmonary TB occur in?
15-20% of immunocompetent patients Up to 50% in people with HIV
37
Where can TB happen in the body?
Anywhere and symptoms depend on location Meningitis Bone and joint Lymph node Genitourinary Pericardial Abdominal
38
How can TB reach other part of the body?
First enters after inhalation Disseminate from the lungs: - spread via the lymphatic system (lymph node TB) - spread via blood stream (meningitis, bone and genitourinary tract)
39
What is does the lymphatic system do?
Maintain fluid balance Defend against infection Facilitate fat absorption in the body Acts as a drainage system, collects excess fluid and waste products from tissues and returns them to bloodstream
40
Describe miliary TB
Disseminated TB spread via the bloodstream Numerous tiny lesions appearing on imaging Severe systemic illness due to bloodstream infection
41
When should active TB be suspected?
In any person who is at high risk of developing TB and has general symptoms of weight loss, fever, night sweats, anorexia or malaise
42
Which patients are high risk of developing TB?
Being born in a high TB prevalence area Children under 5 Close contact with a person with active pulmonary TB History of untreated TB Co-morbid conditions (HIV, diabetes) Immunosuppressive drugs (high dose corticosteroids, chemotherapy) Underserved groups (homeless, people in prisons) History of alcohol excess, injectable drugs, smoking
43
Patients presenting with what should be considered of having pulmonary TB?
Productive cough Breathlessness Haemoptysis
44
Patients presenting with what should be considered of having extrapulmonary TB?
Lymphadenopathy (swelling of lymph nodes) Bone and joint pain Swelling, abdominal or pelvic pain Headache/confusion/changes in balance
45
How should a patient with suspected active TB be investigated?
Initially an x-ray CT imaging Three respiratory samples for microscopy using acid-fast bacilli (AFB)
46
What would the x-ray of someone with active TB look like?
Consolidation mainly within the upper lobes
47
Why are x-rays commonly used?
Rapid and relatively inexpensive way to assess the lungs for abnormalities
48
Why would there be consolidation in the upper lobes?
They have a higher concentration of oxygen More favourable location for TB to thrive
49
Is consolidation specific to TB?
No, it refers to the replacement of air in the alveoli with something else like fluid, inflammatory cells or other material
50
What would a series of Ct images show in a patient with TB?
Shows a 3D image of the lungs Identifies spread of TB and cavities within the lungs Identify involvement of lymph nodes
51
How should the respiratory samples be collected?
Spontaneously produced Deep cough sputum samples Preferably with one early morning sample
52
Why is an early morning sputum sample preferred for TB testing?
They tend to have a higher concentration of bacteria due to overnight accumulation in the lungs. Improves the chances of detecting bacteria through microscopy
53
Describe AFB and what it can't differentiate
A rapid test to identify presence of acid-fast bacteria Not able to differentiate: - Mycobacterium tuberculosis, nontuberculous mycobacteria or other acid-fast bacteria - Dead from live bacteria
54
How does it take for a TB culture to grow?
4-6 weeks
55
Who should be screened for TB?
People who have been in contact with active TB - household members, close contacts Immunocompromised at high risk of reactivation - HIV, solid organ transplant New entrants to UK from high TB prevalence country New employees to NHS Evidence of TB scarring on x-rays (could indicate incomplete treatment) Targeted screening programmes - regions with higher prevalence regions, under-served groups
56
How long after a Mantoux test is the reactive area measured?
48-72 hours
57
What is considered a positive Mantoux result?
5mm or more for those with compromised immune systems or recent exposure to TB 10mm or more for healthcare workers 15mm or more for those with no known risk factors
58
Why would a false-positive Mantoux result occur?
Due to prior BCG vaccination Exposure to non-tuberculous mycobacteria
59
Why would a false-negative Mantoux result occur?
In individuals with weakened immune systems or recent TB infections
60
What are the limitations of the Mantoux test?
Requires two visits Trained personal for administration and interpretation Can't distinguish between active and latent TB
61
What does TGRA stand for?
Interferon gamma release assay
62
What is IGRA?
A blood test used to help diagnose latent TB
63
What does IGRA do?
Detects the body's immune response to TB bacteria Measures amount of IFN-y released
64
What would a positive IGRA result suggest?
The presence of TB bacteria in the body Doesn't distinguish between latent and active TB
65
When infected with TB bacteria, what is released by white blood cells?
Interferon-gamma (IFN-y) in response to antigens
66
How often can TB treatment be administered?
Either taken daily or given three times a week as a supervised therapy
67
What is supervised TB treatment also known as?
Directly Observed Therapy (DOT)
68
Describe supervised TB treatment
A strategy where a healthcare worker or designated individual observes a patient taking their TB medication, ensuring they adhere to prescribed treatment regimen
69
Why is supervised TB treatment a crucial method?
Improves treatment success Prevents drug resistance Reduces transmission of disease
70
What are the 2 phases in standard management of an active TB infection?
Initial phase Continuation phase
71
How long does standard treatment for active TB last?
6 months
72
What drugs are given in the 2 months of initial phase?
Rifampicin Isoniazid + pyridoxine Pyrazinamide Ethambutol
73
What drugs are given in the 4 months of the continuation phase?
Rifampicin Isoniazid + pyridoxine
74
What additional therapies may be used in patients with active TB?
Corticosteroid for TB meningitis or pericarditis Colecalciferol supplementation - vitamin D deficiency is linked to an increased risk and potentially more severe progression of TB. Alternatively, adequate vitamin D levels are associated with enhanced immune responses against mycobacterium tuberculosis Antiemetics - common side effects of TB medicine NRT for smoking cessation Nutritional supplementation in malnourished patients
75
What two regiments are used for latent TB?
Rifampicin and Isoniazid + pyridoxine for 3 months OR Isoniazid + pyridoxine for 6 months
76
What is mono-resistant TB?
Resistance to one of the first-line antimicrobial used in standard TB therapy
77
What is multi-drug resistant TB (MDR-TB)?
There is resistance to both isoniazid and rifampicin
78
What does MDR-TB require?
Longer, more complex, and often more toxic second-line treatment regimens
79
Treatment for resistant TB can only be initiated by who?
TB specialist
80
What are the treatment options for resistant TB?
Various combinations of: Linezolid Clofazimine Bedaquiline Amikacin
81
How to prevent TB
1. Raising and sustaining awareness of TB amongst healthcare professionals, those working within high-risk groups and patients at higher risk 2. Information to the public about TB 3. Vaccination
82
Examples of information given to the public about TB
Recognition of symptoms Understanding transmission Benefits of diagnosis and treatment Location and opening hours of testing services Reducing stigma associated with TB Risk for patient travelling to/from high incidence countries
83
Who should be encouraged to have the BCG vaccine?
Infants Children New entrants
Respiratory
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