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DTMH > Weeks 6-7 > Flashcards

Weeks 6-7 Flashcards

1
Q

What is the main mode of TB resistance transmission?

A

Primary resistance

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2
Q

What are the 3 dimensions of TB disease?

A

Macroscopic pathology
Infectiousness
Symptoms

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3
Q

Is CXR superior to a symptom screen?

A

Yes

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4
Q

What percentage of all prevalent TB is subclinical?

A

50%

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5
Q

What percentage of subclinical TB is smear positive?

A

33%

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6
Q

What is subclinical TB?

A

Macroscopic pathology without symptoms

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7
Q

How is M tuberculosis hominis spread?

A

Inhalation of infected drops
Conjunctiva
Abraded skin

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8
Q

How long is M tuberculosis hominis viable?

A

Dry sputum - weeks
Wet sputum - months

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9
Q

How is M tuberculosis bovis transmitted?

A

Milk from infected cows (eradicated by pasteurisation)

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10
Q

What are symptoms of M tuberculosis bovis infection?

A

Intestinal lesions
Tonsillar lesions

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11
Q

What are the 5 factors of TB pathogenesis?

A
  1. Virulence of bacillus
  2. Induced hypersensitivity
  3. Host immunity
  4. Granulomatous reaction patten
  5. Intracellular bacillus survival
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12
Q

What is the virulence of the TB bacillus directly related to?

A

Lipid fractions within the cell wall

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13
Q

What is responsible for tissue destruction in TB?

A

Hypersensitivity to bacillus
Sensitisation 2-4w post infection
On 1st exposure, non-specific neutrophilic inflammatory response

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14
Q

What does the inflammatory reaction become post sensitisation?

A

Granulomatous

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15
Q

What does a granuloma consist of?

A

Epitheloid histiocytes
Langhan’s multinucleated giant cells
Plump fibroblasts
Lymphocytes

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16
Q

How does TB avoid phagocytosis?

A

Acidification of phagosome via H+-ATPase exclusion
Recruitment of TACO protein prevents delivery to lysosome

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17
Q

How does the presence of iron modify cytokine activity?

A

Decreased TNF secretion
Decreased IL-1 and IL-6 mRNA

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18
Q

Which protein inhibits macrophage apoptosis in TB?

A

Mcl-1

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19
Q

What are the mechanisms of TB to inhibit phagosome-lysosome fusion?

A

Secretion of serine/theanine protein kinase G
Glycoprotein phagosome composition alteration

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20
Q

What is primary TB?

A

TB infection in previously unexposed individual

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21
Q

In which stage of TB is Ghon focus found?

A

Primary TB

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22
Q

Where is Ghon focus found?

A

Area of greatest volume of inspired air
- Lower part of upper lobe
- Upper part of lower lobe

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23
Q

What is a Ghon complex?

A

Ghon focus + lymph node involvement

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24
Q

When does Ghon focus caseate?

A

End of 2nd week

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25
Q

What are the outcomes of primary tuberculosis?

A
  1. Fibrosis and calcification
  2. Progressive pulmonary TB
  3. Transbronchial spread
  4. Lymphatic spread
  5. Haemotogenous spread (miliary TB)
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26
Q

What causes post-primary tuberculosis?

A

Reactivation of latent endogenous infection OR exogenous reinfection

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27
Q

What is the pathogenetic mechanism for post-primary TB?

A

Bronchial obstruction -> lipid pneumonia -> massive necrosis and cystic cavitation

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28
Q

What areas does post-primary TB usually affect?

A

Apical and posterior segments of upper lobe (Simon’s foci)
Superior segment of lower lobe

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29
Q

What are the features of post-primary TB?

A

Apical or posterior segments of one or both upper lobes
Airway obstruction causing lobular lipid pneumonia
Intrapulmonary spread via bronchi
Thin-walled cystic cavitation
1-3cm areas of caseous consolidation 1-2cm beneath pleura
Abundant AFBs
Aerosol formation
Remain localised or progress slowly

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30
Q

What are the outcomes of post-primary TB?

A
  1. Fibrocalcific arrested TB
  2. Progressive pulmonary TB
  3. Pleural effusions, empyema, pleurisy
  4. Endobronchial and endotracheal TB
  5. Intestinal TB
  6. Lymphatic and blood spread with resultant miliary TB
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31
Q

Erosion of which vessels causes TB limited to the lung vs disseminated TB?

A

Pulmonary artery -> limited to lung
Pulmonary vein -> systemic dissemination

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32
Q

Name rare sites for TB

A

Heart
Thyroid
Pancreas
Striated muscle

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33
Q

What is the difference in tuberculomas in children vs adults?

A

Location
Adults - supratentorial
Children - posterior fossa

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34
Q

Why is TB endometritis difficult to diagnose?

A

Granulomata are shed every menses

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35
Q

Describe the progress of renal tuberculosis

A

Lesions in kidney cortex bilaterally -> progress in 1 kidney and stationary in the other -> invades pyramids and calyx walls -> large cavitating mass with shell of normal kidney remaining

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36
Q

How is the performance of LF-LAM as HIV severity increases?

A

More severe HIV, better performance

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37
Q

Which PLHIV should get an LF-LAM?

A

Anyone seriously ill admitted to hospital
Any symptomatic patient
Any patient with CD4<200

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38
Q

What are the advantages of TB culture?

A

Highly sensitive
Low limit of detection

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39
Q

What are the disadvantages of TB culture?

A

TTP
Requires infrastructure

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40
Q

Why must you be careful with a TB NAAT trace result?

A

Detection of MTB DNA at lowest limit of detection - can occur in previously diagnosed/treated

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41
Q

What are the advantages of TB Xpert Ultra?

A

Improved sensitivity
Large PCR reaction volume
Multitarget genetic markers

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42
Q

Which specimens are recommend for Xpert Ultra in children?

A

Stool

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43
Q

What are the common resistance genes seen with rifampicin?

A

rpoB

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44
Q

What are the common resistance genes seen with INH?

A

katG
inhA

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45
Q

What are the common resistance genes seen with bedaquiline?

A

atpE (ATP synthetase)
rv0678 (efflux pump)

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46
Q

Which culture type yields faster DST results?

A

Liquid culture

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47
Q

What does the proportion method mean?

A

If >1% of isolates are resistant, there is acquired resistance

48
Q

Is heteroresistance detected better by Xpert Ultra or LPA?

A

Equal detection

49
Q

What antigens are used in TBSTs and why?

A

Esat6
CFP10
Do not cross react with BCG

50
Q

What are the drug properties of rifampicin?

A

Bactericidal <1 hour
High potency
Most effective sterilising agent

51
Q

What are the target bacilli of rifampicin?

A

All populations including dormant

52
Q

Which drug has an acidic pH?

A

Pyrazinamide
(The rest are alkaline and acidic)

53
Q

Which drug only targets intracellular bacilli?

A

Pyrazinamide

54
Q

What are the drug properties of INH?

A

Bactericidal >24h
High potency

55
Q

What are the target bacilli of INH?

A

Rapid and intermediate growing bacilli

56
Q

What are the drug properties of pyrazinamide?

A

Bactericidal
Low potency (achieves sterilisation within 2-3months)

57
Q

What are the target bacilli of pyrazinamide?

A

Slow growing bacilli

58
Q

What are the drug properties of ethambutol?

A

Bacteriostatic
Low potency
Minimises drug resistance

59
Q

What are the target bacilli of ethambutol?

A

All populations

60
Q

What is the dose for RHZE?

A

150/75/400/275

61
Q

What is the MOA of isoniazid and ethambutol?

A

Inhibition of cell wall synthesis

62
Q

What is the MOA of rifampicin?

A

Inhibits RNA synthesis

63
Q

What is the MOA of pyrazinamide?

A

Disrupts plasma membrane and energy metabolism

64
Q

Are corticosteroids recommended in TBM?

A

Yes, reduces complications

65
Q

How long can the effect of rifampicin last on OCPs post treatment?

A

Up to 2 months

66
Q

How do you manage pre-existing liver disease and TB treatment?

A

Baseline LFTs
Normal = start treatment
Elevated <2xULN = start and monitor
Elevated >2x ULN = liver friendly regimen

67
Q

How do you manage renal dysfunction and TB treatment?

A

Dose adjust ethambutol and pyrazinamide if CrCl <30 or hemodialysis (RHZE 3 days, RH 4 days)

68
Q

When do you repeat sputum testing?

A

End of intensive phase (conversion)
End of treatment (outcome)

69
Q

How do you manage if sputum smear is positive at 7w?

A

Adherence counselling
PCR, culture and DST
Continue with RHZE for 3rd month
Repeat smear at 11w

70
Q

What is the difference between treatment interruption and loss to follow up?

A

Interruption = <2mo (restart where interrupted)
LTFU = >2mo (restart intensive phase)

71
Q

What class of drug is bedaquiline?

A

Diarylquinoline

72
Q

What is the MOA of bedaquiline?

A

Inhibits mycobacterial ATP synthase

73
Q

Can bedaquiline be used in paediatrics?

A

No clinical data but WHO has provided guidelines

74
Q

What drug class if delamanid?

A

Nitro-dihydro-imidazoxazole

75
Q

What is the MOA of delamanid?

A

Inhibits mycolic acid synthesis

76
Q

What WHO category are:
Bedaquiline
Delamanid
Pretomanid

A

Bedaquiline - A
Dalamanid - C
Pretomanid - no category

77
Q

Can delamanid be used in paediatrics?

A

Yes (paediatric doses)

78
Q

What drug class is pretomanid?

A

Nitroimidazole

79
Q

What is the MOA of pretomanid?

A

Inhibits mycolic acid biosynthesis

80
Q

Can pretomanid be used in paediatrics?

A

No established safety in pregnancy/children

81
Q

What is the regimen for DR TB?

A

9 months total
BDQ for 6 months
+ levo, ethambutol, pyrazinamide, ethionamide, INH for 4 months
FOLLOWED BY
levo, ethambutol, pyrazinamide and clofazamine for 5 months

Ethionamide and INH -> clofazamine

82
Q

If patient is suffering from GIT S/E secondary to ethionamide, what can we replace it with?

A

2 months of linezolid 600mg daily

83
Q

What is BPaLL?

A

Bedaquiline
Pretomanid
Linezolid
Levofloxacin

84
Q

What are the side effects of linezolid?

A

Peripheral neuropathy
Myelosuppression

85
Q

If patient is pregnant or <15yo, what do we use for DR TB?

A

BDLL
D = delamanid

86
Q

What is eligibility criteria for BPaLL?

A

Non-pregnant
<15yo
No exposure to BP or linezolid > 1 month

87
Q

How do we manage DR TB if the patient has exposure > 1 month to BP or linezolid?

A

Do resistance testing
If resistance to levo, exclude

88
Q

What must we be cautious with concerning BPaLL and HIV patients?

A

AZT - myelosuppression
EFV - lowers bedaquiline dose

89
Q

When do we repeat smear and culture for DR TB?

A

Initiation
2 weeks
1 month
Monthly until end of treatment

90
Q

When should culture conversion occur by?

A

Month 2
By month 3, take action!

91
Q

What was the Nix study?

A

3 drug regimen BPaL for 26 weeks

92
Q

What was the Zenix trial?

A

Optimising LZD dose

93
Q

What is the issue with patients defaulting on bedaquiline?

A

BQG half life = 5 months
TB monotherapy causes resistance

94
Q

What are the available TPT regimens?

A

3HP
3HR
6H
12H

95
Q

What is 3HP?

A

3 months INH + rifapentin weekly

96
Q

What is 3HR?

A

3 months INH + rifampicin daily

97
Q

What is 6H

A

6 months INH daily

98
Q

What is 12H?

A

12 months INH daily

99
Q

What TPT can we give >15yo with HIV?

100
Q

In which patients on DTG can 3HP be given?

A

VL<50 within last 6 months

101
Q

What TPT can we give <15yo with HIV?

102
Q

What TPT can we give pregnant women with HIV?

103
Q

What TPT can we give >15yo without HIV?

104
Q

What TPT can we give <15yo without HIV?

105
Q

What TPT can we give pregnant women without HIV?

106
Q

What impact does TB coinfection have on ART?

A

Timing of initiation
Drug selection
Drug levels
Adherence
Side effects

107
Q

What is the difference between unmasking IRIS and paradoxical IRIS?

A

Unmasking - TB not known
Paradoxical - TB known

108
Q

Name risk factors for paradoxical TB IRIS

A

Advanced immunosuppression (CD4 <100)
High MTB load
Shorter interval
High baseline inflammation

109
Q

What condition significantly increased paradoxical TB IRIS mortality?

A

CNS involvement

110
Q

What is the clinical manifestation of paradoxical TB IRIS?

A
  1. Lymphadenopathy
  2. Constitutional symptoms
  3. Pulmonary
  4. CNS
  5. Abdominal
111
Q

How do we distinguish TB IRIS from DILI?

A

We can’t!
If severe, treat as DILI and restart ART after TB reinitiation

112
Q

What is the management of mild TB IRIS?

A

Continue ART
Symptomatic treatment
Interventions

113
Q

What is the criteria for steroid use in TB IRIS?

A
  1. TB IRIS likely
  2. Differential excluded
  3. Significant symptoms
114
Q

What is optimal ART timing if CD4>50?

A

Within 8 weeks

115
Q

What is optimal ART timing if CD4<50?

A

Within 2 weeks

116
Q

What is optimal ART timing if CNS TB?

A

Within 4-8 weeks

117
Q

What is the most common cause of clinical deterioration on TB treatment?

A

New AIDS-defining illness

DTMH (5 decks)

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