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
Risk factors of reactivation of TB
HIC Immunosupression - cancer, chemos, steroids, anti-TNF Diabetes, renal failures, IVUDU, malnutrition, GI surgery, silicosis (macrophages dont function), smoking, age and frailty
26
Latent TB infection treatment
3-6 months Isoniazid +/- rifampacin
27
What is main probelm drug in treating TB
Rifampacin - CYP450 inducer
28
Rifampacin drug interactions
Oestrogens - ineffective contraception Corticosteroids Phenytoin - titrate up Sulphonylureas - titrate up Anticoagulants - increase INR monitoring, monitor for VTE
29
What do if on hormonal contraception and treated for TB
Rifampacin will make less effective - make contraceptive ineffective Advise IUD or condoms, incl up to post 4 weeks rifampacin
30
What do if on steroids with rifampacin
Double dose - reduced bioavailability Can cause adrenal crisis if not doubled
31
Mycobacteria features
Bacilli rods 2-4 microns length Cell wall - mycolic acid - high molecular weight lipid - needs special stain
32
What amount mycobacterium required for smear positivity
10,000 bacilli/ml sputum required for smear sputum positicity
33
Stains for mycobacteria
Acid fast stains (bacilli look red) Ziel Nielsson Fluorescent staining
34
How use acid fast stain
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
Flourescent staining how done
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
Ways of performing TB culture
Lowenstein-Jensen - agar + egg based Liquid culture done in tubes in electric cabinets sensors set off alarm when growth detected - in a cord
37
How long do mycobacteria take to culture
3-4 weeks
38
What do mycobacterium colonies look like when cultured
Rough, buff coloured
39
Identification and susceptibility testing for MTB
Manual methods - culturing etc Whole genomic sequencing new - less work, identify new outbreaks of TB
40
Quicker versions of identifying sensitivities in MTB
Whole genomic sequencing PCR - cephid xpert MTB/rifampacin ultra PCR test
41
Benefits of PCR for MTB
- detects MTB and rifampacin resistance Can be done on primary samples and posticie cultured isolate 1.5 hr test in optimum circumstances
42
Test for latent TB
IGRA Detects IG levels - measure of immune response to MTB Quantiferon gold plus test
43
How is quantiferon test (IGRA) undertakne
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
Investigatons if cavity found on CXR
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
How monitor treatment in TB
Gain in weight, improving cough and putum, sputum smear and culture 'conversion' eg smear then culture negative Radiological improvement lags behind clinical
46
What can happen in first 2-6 weeks TB treat
Patient gets paradoxically worse before clinically improving
47
When is TB considered infetious and contact tracing needed
Smear positive
48
Tests can do if no sputum/sputum is negative
BAL Endobrachial US and fine needle aspiration/biopsy of enlarged AP window/left hilar lymph nodes -> cytologial examinaton and TB culture
49
What is DOT and who should be offerednit
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
What vitamin deficinecy is ass w TB
Vitamin D - more severe and increased likelihood TB infection Vit D restricts mycobacteruak strokes Prevent reactivation
51
Pyrazanamide side effects on liver
Acute hepatitis Cholestasis Granulomatous hepatitis
52
What liver markers suggest stopping all TB treatment
ALT >3 x baseline with symptoms >5 x baseline without symptoms Bilirubin rises
53
Risk factors for DILI with TB durgs
Low weight HIV co infection Higher baseline ALP Alcohol intake Most occur acutely after starting HRZ
54
How can restart TB drug treatment
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
When consider continuing treatment w hepatotoxicity and what continue with
2 anti TB drugs of low hepatotoxicity eg ethambutol and streptomycin with or wuthout quinolone eg levofloxacin = monitor LFTs Cutaneous reaction - SAME
56
Treatment for pericardial TB
Steoids reduce mortality - 30mg prednisolone for 3 weeks Surgical drainage of pericardial effusion - pericardiocetnesis