Tuberculosis Flashcards

1
Q

What does smear negative mean

A

Bacteria not seen on plain slide
No stains used yet or grown in culture

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2
Q

Pleural fluid aspirate in TB

A

Lymphocyte predominant
Exudate on Lights criteria

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3
Q

What do to investigate for TB if suspicious

A

CT thorax and BAL

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4
Q

Treatment for TB

A

Rifampacin R
Isoniazid H
Ethambutol E
Pyrazinamide Z
(pyridoxine - B6)
Treat aggressively for 2 months with all
Further 4 months w RH

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5
Q

Why give pyridoxine w TB treatment

A

Prevents peripheral neuropathy from isoniazid
B6

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6
Q

Why does TB take so long to treat

A

Rapid growers - 98% dead in 1 week
Slow growers - weeks to months to die
Sporadic grpwers - months to eradicate

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7
Q

MOA of rifampacin

A

Kills rapid organisms and persisters
Best sterilising drug

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8
Q

Isoniazid MOA

A

Kills rapidly dividing organisms

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9
Q

Pyrazinamide MOA

A

Kills intracellular orgnaisms sequestered in macrophages and lymphocytes
Work better at pH 5.5 (lower) therefore can work in lysosomes)

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10
Q

Function of ethambutol in TB

A

Bacteriastatic - preents further replication of TB
Prevents drug resistant TB developing
Can drop once know that bacteria sensitive to all 3 drugs

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11
Q

Principles of TB treatment

A

Start with all 4 drugs + dont reduce until 2 months treatment and drug sensiticvities avaialble
If fully sensitivie and better change isoniazid and rifampacin for 4 months
If no drug sensiticity - 3rd agent if no recourse to resample
ONLY CNS involvement andates 12 months Rx

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12
Q

What mandates 12 months drug treatment TB

A

CNS involvement eg spinal/choroiditis + tuberculomas/CSF

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13
Q

TB epidemiology

A

Most deaths in low and middle income countries
WHO - END TB strategy, reduce TB death and cases by 90% by 2035

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14
Q

Cause of TB

A

Mycobacterium TB complex
M.tuberculosis is most common
M.bovis
M.africanum - africa
Rare:
M.carnetti - opportunistic
M.microti
M.caprae - spanish domestic animals

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15
Q

Spread of TB

A

Airborne droplet nuclei - cough, sing, smoke, suspended in air for hours
Overrowded living, prisons
Can spread oropharyngeal/GI tract

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16
Q

Symptoms of TB

A

Cough - dry -> yellow watery phlegm+/- blood
Low grade fever
Night sweats
Malaise
Loss of appetite, weight loss -> consumption
Weeks to months
Pleurisy if pleurtitic TB

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17
Q

Clinical signs of TB

A

Often normal
Effusion, crackles, lymphadenopahty, clubbing (rare), hepatomegaly, CNS signs, abdo masses, sinuses, skin TB

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18
Q

Key tests TB

A

CXR
Bloods not often helpful
CT scan
Sputum/pleural fluid/urine, pus, lymph node biospy/CSF LP
TB culture and histology

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19
Q

Why do as many smaples as possible in potential TB

A

As many samples as possible as difficult ot culture

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20
Q

Sites of extrapulmonary TB

A

ANywhere 10-25% of time
PLeura
Lymph nodes
Genitourinary
Bone/joint
CNS eg meningitis
Abdo - ilitis, colitis
Disseminated - miliary (if ruptures - pattern in lungs and liver)
Pericardial
Ocular
Skin

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21
Q

Pathology of TB - stages of infection

A

Primary infection -> primary complex -> either
Subclinical infection (90-95% contained) or clinical symptomas and disease -> primary TB

If subclinical infection -> Latent infection ->
1. Clearance and resolution
2. containment -> persistent latent infection
3. endogenous reactivation -> post primary TB -> miliary TB

Both primary and latent can -> miliary by haemtogenous spread

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22
Q

Contacts w infectious TB

A

Infectious - smear +ve 20-30% close household contacts

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23
Q

Prognosis of TB from infection

A

5% -> active disease within 2 years
5% active disease later in life
More likley if infant, adolescense or old age
Treat latent TB in recent contacts resuces risk of active infection by 2/3
Immunosupressed much higher

24
Q

Key principles TB

A

Early detection
Treat contacts
Treat effectively

25
Q

Risk factors of reactivation of TB

A

HIC
Immunosupression - cancer, chemos, steroids, anti-TNF
Diabetes, renal failures, IVUDU, malnutrition, GI surgery, silicosis (macrophages dont function), smoking, age and frailty

26
Q

Latent TB infection treatment

A

3-6 months
Isoniazid +/- rifampacin

27
Q

What is main probelm drug in treating TB

A

Rifampacin - CYP450 inducer

28
Q

Rifampacin drug interactions

A

Oestrogens - ineffective contraception
Corticosteroids
Phenytoin - titrate up
Sulphonylureas - titrate up
Anticoagulants - increase INR monitoring, monitor for VTE

29
Q

What do if on hormonal contraception and treated for TB

A

Rifampacin will make less effective
- make contraceptive ineffective
Advise IUD or condoms, incl up to post 4 weeks rifampacin

30
Q

What do if on steroids with rifampacin

A

Double dose - reduced bioavailability
Can cause adrenal crisis if not doubled

31
Q

Mycobacteria features

A

Bacilli rods
2-4 microns length
Cell wall - mycolic acid - high molecular weight lipid - needs special stain

32
Q

What amount mycobacterium required for smear positivity

A

10,000 bacilli/ml sputum required for smear sputum positicity

33
Q

Stains for mycobacteria

A

Acid fast stains (bacilli look red)
Ziel Nielsson
Fluorescent staining

34
Q

How use acid fast stain

A

Hot carbol fushin - dark red
Poured over smeared slide
Keep for minute
Wash with acid alcohol
Smear counter stained w methylene blue - other cells blue, light blue background
Seen under light microscope with oil immersion lens

35
Q

Flourescent staining how done

A

Auromine-phenol stain is poured over smeared slide, kept for 15 mins washed w acid alcohol, stained w thiazine red
Mycobacteria fluoresce brigh tgreenish yellow on fluroscent microscope

36
Q

Ways of performing TB culture

A

Lowenstein-Jensen - agar + egg based
Liquid culture done in tubes in electric cabinets sensors set off alarm when growth detected - in a cord

37
Q

How long do mycobacteria take to culture

A

3-4 weeks

38
Q

What do mycobacterium colonies look like when cultured

A

Rough, buff coloured

39
Q

Identification and susceptibility testing for MTB

A

Manual methods - culturing etc
Whole genomic sequencing new - less work, identify new outbreaks of TB

40
Q

Quicker versions of identifying sensitivities in MTB

A

Whole genomic sequencing
PCR - cephid xpert MTB/rifampacin ultra PCR test

41
Q

Benefits of PCR for MTB

A
  • detects MTB and rifampacin resistance
    Can be done on primary samples and posticie cultured isolate
    1.5 hr test in optimum circumstances
42
Q

Test for latent TB

A

IGRA
Detects IG levels - measure of immune response to MTB
Quantiferon gold plus test

43
Q

How is quantiferon test (IGRA) undertakne

A

4 tubes - one negative control, one positive, one detects CD4/CD8 response and one tube to detect CD4 response
Uses TB antigen - ESAT 6 + CFP10 generate cell mediated response for release of Interferon gamma
Indicates if been exposed to TB

44
Q

Investigatons if cavity found on CXR

A

FBC, U+Es, LFTs, bone profile, CRP/ESR
Blood borne virus screen - Hep B/C/HIV
Sputum x 3 for AFB smear/TB culture and routine M, C and S
CT scan not indicated at this stage

45
Q

How monitor treatment in TB

A

Gain in weight, improving cough and putum, sputum smear and culture ‘conversion’ eg smear then culture negative
Radiological improvement lags behind clinical

46
Q

What can happen in first 2-6 weeks TB treat

A

Patient gets paradoxically worse before clinically improving

47
Q

When is TB considered infetious and contact tracing needed

A

Smear positive

48
Q

Tests can do if no sputum/sputum is negative

A

BAL
Endobrachial US and fine needle aspiration/biopsy of enlarged AP window/left hilar lymph nodes -> cytologial examinaton and TB culture

49
Q

What is DOT and who should be offerednit

A

Directly observed therapy
do not adhere to treatment (or have not in the past)
have been treated previously for TB
have a history of homelessness, drug or alcohol misuse
are currently in prison, or have been in the past 5 years
have a major psychiatric, memory or cognitive disorder
are in denial of the TB diagnosis
have multidrug‑resistant TB
request directly observed therapy after discussion with the clinical team
are too ill to administer the treatment themselves

50
Q

What vitamin deficinecy is ass w TB

A

Vitamin D - more severe and increased likelihood TB infection
Vit D restricts mycobacteruak strokes
Prevent reactivation

51
Q

Pyrazanamide side effects on liver

A

Acute hepatitis
Cholestasis
Granulomatous hepatitis

52
Q

What liver markers suggest stopping all TB treatment

A

ALT >3 x baseline with symptoms
>5 x baseline without symptoms
Bilirubin rises

53
Q

Risk factors for DILI with TB durgs

A

Low weight
HIV co infection
Higher baseline ALP
Alcohol intake
Most occur acutely after starting HRZ

54
Q

How can restart TB drug treatment

A

Wait until other clinical pictures resolved
Sequentially reintroduve TB drugs at full dose over period of no more than 10 dyas, start with ethambutol or isoniazid with pyridoxine or rifampacin

55
Q

When consider continuing treatment w hepatotoxicity and what continue with

A

2 anti TB drugs of low hepatotoxicity eg ethambutol and streptomycin with or wuthout quinolone eg levofloxacin = monitor LFTs
Cutaneous reaction - SAME

56
Q

Treatment for pericardial TB

A

Steoids reduce mortality - 30mg prednisolone for 3 weeks
Surgical drainage of pericardial effusion - pericardiocetnesis