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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
What are the outcomes of primary tuberculosis?
1. Fibrosis and calcification 2. Progressive pulmonary TB 3. Transbronchial spread 4. Lymphatic spread 5. Haemotogenous spread (miliary TB)
26
What causes post-primary tuberculosis?
Reactivation of latent endogenous infection OR exogenous reinfection
27
What is the pathogenetic mechanism for post-primary TB?
Bronchial obstruction -> lipid pneumonia -> massive necrosis and cystic cavitation
28
What areas does post-primary TB usually affect?
Apical and posterior segments of upper lobe (Simon's foci) Superior segment of lower lobe
29
What are the features of post-primary TB?
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
30
What are the outcomes of post-primary TB?
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
31
Erosion of which vessels causes TB limited to the lung vs disseminated TB?
Pulmonary artery -> limited to lung Pulmonary vein -> systemic dissemination
32
Name rare sites for TB
Heart Thyroid Pancreas Striated muscle
33
What is the difference in tuberculomas in children vs adults?
Location Adults - supratentorial Children - posterior fossa
34
Why is TB endometritis difficult to diagnose?
Granulomata are shed every menses
35
Describe the progress of renal tuberculosis
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
36
How is the performance of LF-LAM as HIV severity increases?
More severe HIV, better performance
37
Which PLHIV should get an LF-LAM?
Anyone seriously ill admitted to hospital Any symptomatic patient Any patient with CD4<200
38
What are the advantages of TB culture?
Highly sensitive Low limit of detection
39
What are the disadvantages of TB culture?
TTP Requires infrastructure
40
Why must you be careful with a TB NAAT trace result?
Detection of MTB DNA at lowest limit of detection - can occur in previously diagnosed/treated
41
What are the advantages of TB Xpert Ultra?
Improved sensitivity Large PCR reaction volume Multitarget genetic markers
42
Which specimens are recommend for Xpert Ultra in children?
Stool
43
What are the common resistance genes seen with rifampicin?
rpoB
44
What are the common resistance genes seen with INH?
katG inhA
45
What are the common resistance genes seen with bedaquiline?
atpE (ATP synthetase) rv0678 (efflux pump)
46
Which culture type yields faster DST results?
Liquid culture
47
What does the proportion method mean?
If >1% of isolates are resistant, there is acquired resistance
48
Is heteroresistance detected better by Xpert Ultra or LPA?
Equal detection
49
What antigens are used in TBSTs and why?
Esat6 CFP10 Do not cross react with BCG
50
What are the drug properties of rifampicin?
Bactericidal <1 hour High potency Most effective sterilising agent
51
What are the target bacilli of rifampicin?
All populations including dormant
52
Which drug has an acidic pH?
Pyrazinamide (The rest are alkaline and acidic)
53
Which drug only targets intracellular bacilli?
Pyrazinamide
54
What are the drug properties of INH?
Bactericidal >24h High potency
55
What are the target bacilli of INH?
Rapid and intermediate growing bacilli
56
What are the drug properties of pyrazinamide?
Bactericidal Low potency (achieves sterilisation within 2-3months)
57
What are the target bacilli of pyrazinamide?
Slow growing bacilli
58
What are the drug properties of ethambutol?
Bacteriostatic Low potency Minimises drug resistance
59
What are the target bacilli of ethambutol?
All populations
60
What is the dose for RHZE?
150/75/400/275
61
What is the MOA of isoniazid and ethambutol?
Inhibition of cell wall synthesis
62
What is the MOA of rifampicin?
Inhibits RNA synthesis
63
What is the MOA of pyrazinamide?
Disrupts plasma membrane and energy metabolism
64
Are corticosteroids recommended in TBM?
Yes, reduces complications
65
How long can the effect of rifampicin last on OCPs post treatment?
Up to 2 months
66
How do you manage pre-existing liver disease and TB treatment?
Baseline LFTs Normal = start treatment Elevated <2xULN = start and monitor Elevated >2x ULN = liver friendly regimen
67
How do you manage renal dysfunction and TB treatment?
Dose adjust ethambutol and pyrazinamide if CrCl <30 or hemodialysis (RHZE 3 days, RH 4 days)
68
When do you repeat sputum testing?
End of intensive phase (conversion) End of treatment (outcome)
69
How do you manage if sputum smear is positive at 7w?
Adherence counselling PCR, culture and DST Continue with RHZE for 3rd month Repeat smear at 11w
70
What is the difference between treatment interruption and loss to follow up?
Interruption = <2mo (restart where interrupted) LTFU = >2mo (restart intensive phase)
71
What class of drug is bedaquiline?
Diarylquinoline
72
What is the MOA of bedaquiline?
Inhibits mycobacterial ATP synthase
73
Can bedaquiline be used in paediatrics?
No clinical data but WHO has provided guidelines
74
What drug class if delamanid?
Nitro-dihydro-imidazoxazole
75
What is the MOA of delamanid?
Inhibits mycolic acid synthesis
76
What WHO category are: Bedaquiline Delamanid Pretomanid
Bedaquiline - A Dalamanid - C Pretomanid - no category
77
Can delamanid be used in paediatrics?
Yes (paediatric doses)
78
What drug class is pretomanid?
Nitroimidazole
79
What is the MOA of pretomanid?
Inhibits mycolic acid biosynthesis
80
Can pretomanid be used in paediatrics?
No established safety in pregnancy/children
81
What is the regimen for DR TB?
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
If patient is suffering from GIT S/E secondary to ethionamide, what can we replace it with?
2 months of linezolid 600mg daily
83
What is BPaLL?
Bedaquiline Pretomanid Linezolid Levofloxacin
84
What are the side effects of linezolid?
Peripheral neuropathy Myelosuppression
85
If patient is pregnant or <15yo, what do we use for DR TB?
BDLL D = delamanid
86
What is eligibility criteria for BPaLL?
Non-pregnant <15yo No exposure to BP or linezolid > 1 month
87
How do we manage DR TB if the patient has exposure > 1 month to BP or linezolid?
Do resistance testing If resistance to levo, exclude
88
What must we be cautious with concerning BPaLL and HIV patients?
AZT - myelosuppression EFV - lowers bedaquiline dose
89
When do we repeat smear and culture for DR TB?
Initiation 2 weeks 1 month Monthly until end of treatment
90
When should culture conversion occur by?
Month 2 By month 3, take action!
91
What was the Nix study?
3 drug regimen BPaL for 26 weeks
92
What was the Zenix trial?
Optimising LZD dose
93
What is the issue with patients defaulting on bedaquiline?
BQG half life = 5 months TB monotherapy causes resistance
94
What are the available TPT regimens?
3HP 3HR 6H 12H
95
What is 3HP?
3 months INH + rifapentin weekly
96
What is 3HR?
3 months INH + rifampicin daily
97
What is 6H
6 months INH daily
98
What is 12H?
12 months INH daily
99
What TPT can we give >15yo with HIV?
3HP 12H
100
In which patients on DTG can 3HP be given?
VL<50 within last 6 months
101
What TPT can we give <15yo with HIV?
6H
102
What TPT can we give pregnant women with HIV?
12H
103
What TPT can we give >15yo without HIV?
3HP 3RH 6H
104
What TPT can we give <15yo without HIV?
3RH
105
What TPT can we give pregnant women without HIV?
3RH 6H
106
What impact does TB coinfection have on ART?
Timing of initiation Drug selection Drug levels Adherence Side effects
107
What is the difference between unmasking IRIS and paradoxical IRIS?
Unmasking - TB not known Paradoxical - TB known
108
Name risk factors for paradoxical TB IRIS
Advanced immunosuppression (CD4 <100) High MTB load Shorter interval High baseline inflammation
109
What condition significantly increased paradoxical TB IRIS mortality?
CNS involvement
110
What is the clinical manifestation of paradoxical TB IRIS?
1. Lymphadenopathy 2. Constitutional symptoms 3. Pulmonary 4. CNS 5. Abdominal
111
How do we distinguish TB IRIS from DILI?
We can't! If severe, treat as DILI and restart ART after TB reinitiation
112
What is the management of mild TB IRIS?
Continue ART Symptomatic treatment Interventions
113
What is the criteria for steroid use in TB IRIS?
1. TB IRIS likely 2. Differential excluded 3. Significant symptoms
114
What is optimal ART timing if CD4>50?
Within 8 weeks
115
What is optimal ART timing if CD4<50?
Within 2 weeks
116
What is optimal ART timing if CNS TB?
Within 4-8 weeks
117
What is the most common cause of clinical deterioration on TB treatment?
New AIDS-defining illness

DTMH (5 decks)

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