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Respiratory > Tuberculosis > Flashcards

Tuberculosis Flashcards

1
Q

Who does TB typically affect?

A

Non-UK born/recent imigrants - south asia, sub-saharan africa
HIV/other immunocompromised conditions (cancer)
Homlessness
Drug use (IV)
Prisoners
Close contacts of TB
Young adults (and elderly)

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2
Q

Age group with highest TB prevalence in Non UK born vs UK born

A

Non-UK born -peak from 25-44 years
UK - above 65 is more prevalent

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3
Q

What microbe causes Tb?

A

Mycobacterium tuberculosis complex

Mycobacterium tuberculosis - MOST
Mycobacterium bovis - cattle and human
Mycobacterum africanum - Africa mostly

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4
Q

What are the characteristics of mycobacterium tuberculosis?

A

Non-motile rod shaped bacteria
Obligate aerobe

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5
Q

What is mycobacterium tuberculosis cell wall like? and what does this allow?

A

Long chain fatty (mycolic) acids
Complex waxes
Glycolipids
=
Structural rigidity
Staining characteristics
Acid-alcohol fast
Survival inside macrophage

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6
Q

What does acid-alcohol fast mean?

A

Physical property that gives a bacterium the ability to resist decolorization by acids/alcohol during staining procedures.

This means that once the bacterium is stained, it cannot be decolorized using acids routinely used in the process

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7
Q

Growth of Tb

A

Slow-growing compared to other bacteria - takes 2-6 weeks to culture and 12-20rhs to divide

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8
Q

How is Tb transmitted?

A

Respiratory droplets - coughing/sneezing

Droplet nuclei are suspended in air and then reach lower airway

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9
Q

Infectious dose of Tb

A

1-10 bacilli - very low dose needed

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10
Q

Is Tb contagious and easy to acquire?

A

Tb is contagious but it is NOT easy to acquire an infection

Need prolonged exposure usually (at least 8 hours/day for 6 months so eg family member, work, school)

Can have casual contact spread eg on the bus but this is rarer

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11
Q

Steps of Tb spread

A

Source case –>
Aerolisation –> (via cough or sneeze)
Airbourne survival –> (droplet size)
Exposure and Inhalation –> (ventilation, proximity to source, duration)
Susceptibility for infection (macrophage function and mucosal immunity)

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12
Q

Pathogenesis of Tb

A

Inhaled aerosols are engulfed by alveolar macrophages
Tb spread via macrophages to local lymph nodes
Primary (Gohn) complex formed - Gohns focus (granuloma) and draining lymph node involvement

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13
Q

What are the next possible steps once Gohn complex has occured?

A

Progression to active disease = Primary infection (only 5%)

OR

Initial containment of infection - latent infection (95%)

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14
Q

What can occur in latent infections?

A

Can heal/self cure - most people (95%)

Can get post primary (secondary) Tb due to reactivation of Tb

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15
Q

What happens when primary complex forms?

A

T helper cells activate macrophages enabling them to become bactericidal and kill TB

Interferon gamma is produced by lymphocytes and is critical for activating macrophages

T lymphocytes can then recognise TB if you have been infected

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16
Q

Two forms of TB infection

A

Subclinical infection - latent TB, reservoir of POTENTIAL disease (90%)

Clinical infection - active TB (10%

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17
Q

Risk factors for reactivation of latent infection of Tb

A

Infection with HIV
Substance abuse
Corticosteroids prolonged use
Immunosuppressive therapy - eg chemotherapy
Tumour necrosis factor alpha (TNFa) antagonists
Organ transplant
Haematological malignancy
Severe kidney disease/dialysis
Diabetes mellitus
Low body weight

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18
Q

What must all suspected and confirmed cases of Tb have?

A

A HIV test - its not easy to be infected with Tb, can be a sign of immunosupression

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19
Q

Latent Tb vs Active Tb

A

Latent:
Inactive, contained bacilli in body (dormant)
CXR normal
Sputum smears and cultures -ve
No symptoms
NOT infectious
Not a case of TB

Active:
Active multiplying bacilli in body
CXR abnormal
Sputum smears/cultures may be +ve
Cough, fever weight loss symptoms
Infectious before treatment
CASE of TB

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20
Q

What do both latent and active Tb have?

A

A positive tuberculin skin test or interferon-gamma test - as both have T cells that are sensitive to TB antigens

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21
Q

Location of Tb most common

A

Lungs - pulmonary Tb

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22
Q

Extrapulmonary cases of Tb

A

Larynx
Lymph nodes
Pleura
Brain
Kidneys
Bones/joints

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23
Q

In who are extrapulmonary Tb cases found in

A

HIV infected or other immunosupressed people
Children

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24
Q

What is miliary TB?

A

Extent spread of Tb carried around the body via blood (lymphatics drain to venous blood then back to lungs)
Resulting in small foci deposits in tissues giving viscera a grainy appearance esp on CXR

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25
Q

Who does miliary TB occur in?

A

Rare - HIV. malnourished children

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26
Q

What does Tb look like on CXR?

A

Consolidation - apex of lung usually

Can have gohn focus (white area where granuloma is present)
Can have lymph node involvement
These two together are gohn complex

Extensive disease:
Cavitation within consolidation and fibrosis
Effusion

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27
Q

Histology of Tb

A

Langherhan giant cells - peripheral nuclei, horse shoe shape

Caseating granuloma - central necrosis surrounded by inflammatory immune cells eg lymphocytes, giant cells - epithelioid macrophages

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28
Q

Constitutional (whole body) symptoms of Tb

A

Unexplained fever
Weight loss
Loss of appetite
Night sweats
Tiredness/malaise

RARELY acute - usually subacute/chronic

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29
Q

Respiratory symptoms of TB

A

Cough
Haemoptysis
Breathlessness if pleural effusion

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30
Q

Auscultation of Tb

A

Crackles in affected area, but often no chest signs

31
Q

3 investigations for pulmonary Tb

A

CXR
Samples for microbiology - sputum
Histology - biopsy to see granuloma etc

32
Q

What part of lung is often involved in TB and why?

A

Apex of the lung - Tb is obligate aerobe, apex is well oxygenated and can survive well here

33
Q

Microscopy methods for testing Tb

A

Sputum staining with:
Ziehl Neelsen (pink bacilli = Tb)
or
Auramine stain with fluorescent microscope (yellow bright bacilli = Tb)

34
Q

Positives and negative of microscopy staining to diagnose Tb

A

Rapid, cheap

Sensitivity is not great so need lots of TB in mucus to be +ve - therefore if +ve this means pt is likely infectious

35
Q

Negatives of microscopy staining to diagnose Tb

A

Cannot differentiate mycobacterium tuberculosis from non-tuberculous mycobacterium
(both acid/alcohol fast organisms)

Cannot differentiate live and dead organisms

36
Q

What is the gold standard for Tb diagnosis?

A

TB culture - one of the MOST sensitive methods

37
Q

Examples of TB cultures

A

Lowenstein Jenson slopes
Automated culture technology

38
Q

Problem with Tb culture

A

TAKES TIME - slow growing organism

39
Q

What else can be used to detect TB and allow tailoring of treatment?

A

Nucleic acid detection tests eg NAAT - nucleic acid amplification tests
Or whole genome sequencing

Allow rapid diagnosis and monitor drug resistance mutations - can then tailor treatment

40
Q

How do we diagnose latent Tb?

A

Tuberculin sensitivity test
Interferon gamma assays

41
Q

How does tuberculin sensitivity test work?

A

Cell-mediated immune response in the form of delayed hypersensitivity reaction to a purified protein derivative (PPD) of mycobacterium tuberculoisis (tuberculin)

Tuberculin is injected intradermally and then site is measured 48-72hrs later to see reaction on skin (redness, etc)

42
Q

Problems with tuberculin skin testing

A

False positives from BCG vaccine, non TB mycobacterium
False negatives from immunocompromised, HIV, drugs, advanced disease
Subjective interpretation

43
Q

Positives of tuberculin skin test

A

Cheap
Laboratory not needed
Evidence of latent disease allows prediction of progression to active

44
Q

What is an interferon gamma assay?

A

Laboratory test
T cell based assay - see if there are T cells in pts blood that are reactive to TB antigens.
Expose pt blood to TB antigens and measure interferon gamma (cytokine)

45
Q

What is the good thing about interferon gamma releasing assays?

A

No cross reaction with BCG

46
Q

4 first line medications for TB

A

Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
(RIPE)

47
Q

Principles of TB treatment

A

EARLY and ADEQUATE - with multiple anti-TB drugs
Close monitoring for compliance
Prevent secondary transmissions and cases

48
Q

Why is Tb treated with multiple drugs?

A

Tb is difficult to kill
When there are mutations, drug resistance can occur so need to use multiple drugs to ensure that mutated species do not survive and multiply

49
Q

Side affects of Rifampicin drugs

A

Rifampicin - raised transaminases and induces CYP450
Orange urine and secretions

50
Q

Side effects of isoniazid

A

Peripheral neuropathy (give pyridoxine 10mg which is Vit B6)
Hepatotoxicity

51
Q

Side effects of pyrazinamide

A

Hepatotoxicity

52
Q

Side effects of ethambutol

A

Visual disturbance

53
Q

What else is given alongside multipdrug therapy for Tb?

A

Vitamin D - deficiency is associated
Potential surgery

54
Q

Treatment for pulmonary Tb length

A

3 or 4 drugs for 6 months
Then Rifampicin and Isoniazid for 3 months

55
Q

Treatment duration for CNS involved Tb

A

18 months treatment

56
Q

How is adherence to Tb medication ensured?

A

Direct observed therapy - take infront of someone
Video observed therapy -ensures compliance and reduces resistance and poor outcomes

57
Q

Ways Tb resistance can occur

A

Multiplication = spontaneous resistant mutations
If have improper regime or poor drug compliance, diagnostic delays, overcrowding then there is selection for these mutations
= resistance

58
Q

Types of resistant tb?

A

Multi-drug resistant Tb - resistant to rifampicin and isoniazid (these are 2 first-line drugs)

Extremely drug-resistant - also resistant to fluoroquinolones and at least 1 injectable

59
Q

When is likelihood of Tb resistance increased?

A

Previous Tb treatment
HIV
Known multi-resistant drug contact

60
Q

When can miliary tuberculosis occur?

A

Primary infection or during reactivation - Bacteria draining to lymph enter venous system and circulate back to lungs

61
Q

What is always involved in miliary Tb?

A

Lungs ALWAYS involved
Fever
Very unwell
Dry cough
Often multiple organs involved

62
Q

What can suggest involvement of other organs with miliary Tb?

A

Headaches - meningeal involvement
Pericardial, pleural effusions
Ascites - peritoneum involvement
Retinal involvement - choroid tubercles on eye

63
Q

What extrapulmonary tb is common in children?

A

Lymphadenitis - lymph node involvement

64
Q

What occurs in lymphadenitis?

A

Cervical lymph nodes most common
Abscesses and sinuses involvement
Neck tuberculosis - scrofula

65
Q

What happens in genitourinary tuberculosis?

A

Slow progression to renal disease
Spreading to lower urinary tract

66
Q

What is the most common bone and joint Tb?

A

Spinal TB - Potts disease

67
Q

Signs/symptoms of tuberculosis meningitis

A

Chronic headache
Fever
CSF - raised proteins, lymphocytosis

68
Q

How do we prevent tuberculosis?

A

Notifiable disease - have to inform public health England
Then can do contact tracing and monitor
BCG vaccine

69
Q

How is an infected person with Tb controlled?

A

PPE
Negative pressure isolation
Sideroom

70
Q

BCG vaccine good?

A

Given to babies in high prevalence communities - not routine
Little evidence in protecting adults as protection wanes

71
Q

What do you always have to consider when giving BCG vaccine?

A

It is a live vaccine so have to consider HIV testing prior as cannot have if have HIV

72
Q

What is the gohns focus vs gohns complex?

A

Gohns focus - sub pleural focus of tubercles (caseating granuloma)

Gohns compelx - gohns focus + draining (hilar) lymph nodes together

73
Q

Active Tb infection tests

A

Acid-fast smear and cultures of sputum
Sputum culture most sensitive (may take 1-3 weeks or 4-8 depending on medium)

Respiratory (21 decks)

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