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TB Flashcards

1
Q

What proportion of patients with HIV are TB +ve?

A

Around 25%

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2
Q

What proportion of TB is MDR/XR?

A

5%/0.5%
??????

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3
Q

What strategies can be employed to decrease the risk of TB transmission in hospital settings?

A

Open windows, high ceilings, UV light, NP95 masks

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4
Q

What is the risk of developing active TB from latent TB?

A

5-10%

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5
Q

Who should be tested for latent TB?

A

3 groups: Active TB contacts, current HIV immunosuppression, other high risk groups: endemic, homeless, healthworkers.

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6
Q

When is a TST positive?

A

5mm classified as positive in HIV or recent contact.
10 mm classified as positive in recent arrivals from high risk countries, healthcare workers, prisoners, homeless, drug users, immigrants
15mm in other general population

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7
Q

Name 5 symptoms of pulmonary TB

A

Fever
Night sweats
Weight loss, anorexia
Fatigue
Cough with productive sputum
Haemoptysis seen in advanced disease

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8
Q

What % of TB is pulmonary?

A

80-85%

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9
Q

What are the most common sites of extrapulmonary TB?

A

Lymphadenitis
Pleural
Urogenital
Bone and joint disease
GI
CNS
Cutaneous
Pericardial

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10
Q

What proportion of TB is pulmonary/extra pulmonary in HIV patients?

A

Pulmonary 40%
EPTB 30-40%
Pulmonary + EPTB 20-30%

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11
Q

How does TB lymphadenitis present?

A

> 90% occur in head and neck lymph nodes
HIV negative
Painless lymphadenopathy without systemic symptoms – NO FEVER
Only 20-30% have an abnormal CXR
(HIV patients - fever more common)

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12
Q

What are the patterns of cutaneous TB disease?

A

Primary cutaneous – direct inoculation into skin from exogenous source
- Ulcer (TB chancre)
- TB verrucose cutis (‘TB wart’)
- PPD usually negative

Secondary cutaneous - PPD usually positive + can detect AFB in lesion. More common sec than primary.

Tuberculids

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13
Q

How does secondary cutaenous TB present?

A

Scrofuloderma - from direct extension of underling TB in lymph node / bone / joints
Acute haematogenous papules and pustules
Lupus vulgaris – multiple nodules and plaques on face and neck
TB gumma – multiple soft tissue abscess
Sinus tract

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14
Q

How may cutaenous tuberculids present?

A

Tuberculids - Cutaenous hypersensitivity reactions (AFB not in lesion), PPD +ve
Erythema induratum (Bazin disease) - recurrent nodules on back of legs
Papulo-necrotic tuberculids - crops of recurrent skin papules
Lichen scrofuloderma - extending eruption of follicular papules in children with TB
Erythema nodosum (primary / secondary)

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15
Q

Where does musculoskeletal TB most often occur?

A

Thoracic spine (Lumbar = brucellosis)

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16
Q

Differentiate brucella in the spine vs TB

A

Spinal TB - Visible abscess with destruction of vertebrae
Brucellosis – lumbar spine with anterior superior bone erosion

TB - common, young adults, thoracic, lytic lesions
Brucella - not common, older adults, lumbar, blastic lesions anterior V body

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17
Q

What is the most common presentation of urinary TB?

A

Aseptic pyuria

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18
Q

How can you diagnose genitourinary TB?

A

PPD >95% +ve
AFB in urine 80%
Culture >95%

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19
Q

How does TB meningitis present?

A

Meningitis with stupor and cranial nerve involvement is classic presentation

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20
Q

What is the CSF LP findings in TB?

A

Increase WCC (mononuclear - lymphocytic), low glucose, high protein

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21
Q

How can you definitively diagnose TB meningitis?

A

CSF AFB smear- sensitivity 10-30%
CSF-Xpert 60% sensitive
Xpert-CSF Centrifugated: 82% sensitive
Culture -66% sensitive

Also CXR, sputum AFB smear/culture

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22
Q

What is the WHO recommendation for testing for active TB?

A

All patients with cough >2wks should have TB screen with sputum x3 for AFB

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23
Q

What does ‘acid fast bacilli’ mean?

A

tubercle bacilli are identifiable from nearly all other species of bacteria by their ability to resist decolouration with weakly acidified alcohol

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24
Q

What types of gram stain are possible for TB?

A

Ziehl-Neelsen (ZN), fluorescence microscopy (auramine)

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25
What is the sensitivity of AFB smear, and how can this be increased?
Sensitivity of AFB smear is 50-60% - Fluorescence microscopy is 10% more sensitive than conventional, and has reduced reading time. - Centrifugation increases sensitivity by 10%
26
What are the disadvantages of gram stain microscopy for acid fast bacilli?
- Requires 10,000 organisms/ml to be positive (low sensitivity) - Patient can be very unwell / infect others by time smear is + - No differentiation between TB/NTM
27
Name the test and the organism?
TB, Ziehl Neelson stain
28
Name the features of TB on CXR
Mediastinal-hilar lymphadenopathy Alveolar-interstitial pattern Reactivation - more peri hilar and upper lobe Primary disease - middle and lower lobes
29
What is the gold standard for TB diagnosis?
Culture (detect as low as 100 AFB/ml), also provides DST
30
What different types of culture are available for TB?
Solid media: - Lowenstein-Jensen (LJ) or Ogawa - Good media but very slow (2-4wks) - Malachite green prevents growth of contaminants Advantages: less contamination Disadvantages: very slow (2-4wk for positive, 8wks for negative) Liquid media: 7H9 MGIT (mycobacterial growth indicator tube) - More sensitive than solid media - Uses fluorescence to detect oxygen consumption by bacterial growth - ZN stain confirms presence of mycobacteria – cordons are characteristic of MTB Advantages: more sensitive, much faster (10-14 days for positive) Disadvantages: more expensive, more contamination
31
What is the organism? Which test? Why?
TB - ZN stain – cordons characteristic of MTB
32
How many organisms need to be present in a sample for molecular tests to be positive?
Gene Xpert needs 150 bacilli to be positive Culture detects as low as 100 bacilli / ml Ultra Gene Xpert needs 10 bacilli to be positive Smear needs 10,000 bacilli to be positive
33
What gene does Gene Xpert test for mutations in for rifampicin resistance?
rpoB gene
34
What samples can be used for TB gene Xpert?
sputum, CSF, ascites, pleural fluid, lymph node aspirate Lymph node aspirate / tissue: good sensitivity (85%) CSF: good sensitivity (80%) Pleural fluid: poor sensitivity (45%) Gastric lavage (?only infants): 84%
35
How sensitive and specific is gene Xpert?
High sensitivity (98%) and specificity (99%), result in 2 hrs
36
What is urine LAM? In which group of patients is it useful in?
Lipoarabinomannan (LAM) - polysaccharide in mycobacterial cell wall HIV positive
37
How do you diagnose pleural TB?
Culture of pleural biopsy 86% sensitive Culture of pleural aspirate 35% sensitive Smear of pleural aspirate 10-30% sensitive
38
How useful is gene Xpert for diagnosis of TB meningitis from CSF?
CSF AFB smear- sensitivity 10-30% CSF-Xpert 60% sensitive culture 66% sensitive Xpert-CSF Centrifugated: 82% sensitive
39
Who do you test for latent TB?
Who to test and treat Definitely HIV infected Contacts of pulmonary TB Anti-TNF treatment Transplant candidates Silicose Consider Prisoners Healthcare workers Immigrants from high TB burden country Homeless IVDU
40
What are the treatment options for latent TB?
6 months of daily isoniazid (WHO) 3-4 months of weekly rifapentine plus isoniazid in high incidence settings 3-4 months of isoniazid plus rifampicin daily (alternative to 1, for children and adolescents in high incidence countries) 3 or 4 months rifampicin alone daily (only in low incidence countries)
41
What is the definition of TB monoresistance?
Resistance to a single drug
42
What is the definition of TB polyresistance?
Multiple drug resistance that does not constitute MDR/XDR
43
What is the definition of MDR TB?
Resistance to Rifampicin and Isoniazid (at least)
44
What is the definition of RR TB?
Rifampicin resistant TB. 90% of cases resistant to Rif will be resistant to INH
45
What is the definition of XDR TB?
MDR TB (INH and Rif resistance) plus resistance to a fluoroquinolone and at least one other group A drug
46
What is the definition of pre XDR TB?
MDR TB (INH and Rif resistance) plus resistance to a fluoroquinolone (Only XDR if also resistant to one other group A drug)
47
What is first line Rx for drug sensitive TB?
4 drugs for 2 months – HRZE (Rifampicin, Isoniazide, Pyrazinamide, Ethambutol) - INTENSIVE PHASE 2 drugs for 4 months – HR (INH, RIF) - CONTINUATION PHASE Daily therapy is optimal, but 3x/wk therapy is acceptable alternative if DOT (directly observed therapy) and not HIV+
48
What is an alternative regimen to HRZE 2x4 for treatment of drug susceptible TB?
4-month regimen of isoniazid, rifapentine, moxifloxacin and pyrazinamide (2HPMZ/2HPM) 4-month regimen of isoniazid, rifapentine, pyranzinamide, ethambutol (2HRZ(E)/2HR) Have to be greater than 12 yo and >40kg
49
Drug susceptible TB: when would you extend treatment greater than 6 months?
Pulmonary TB - cavitating disease. Not in guidelines but often extended to 9 months. Bone, CNS. 9-12 months. (2 months intensive, 10 months maintenance)
50
How do you monitor for response to TB treatment?
Assess response to treatment with 3 methods - Clinical evaluation: symptoms, clinical improvement (monthly) - Bacteriologic evaluation: smear, culture (at 2 months) - CXR (no set guidance)
51
What is the definition of TB treatment failure as per WHO?
WHO define treatment failure as lack of conversion by 5 months
52
What would you do if a patient is still smear positive at 2 months post Rx for TB?
- Recheck at end of month 3 - If still positive - do repeat culture and DST Changing Rx depends on symptoms, clinical assessment and DST/resistance
53
Who would you administer steroids to with TB Rx?
CNS TB Pericardial TB
54
What is first line Rx for TB in pregnancy?
HRZE 4x2 (same) Breastfeeding also safe Rule out TB in baby followed by 6 months of INH
55
Which TB drugs cause hepatotoxicity?
Rifampicin - early Isoniazid - anytime Pyrazinamide - late (end of intensive phase)
56
What is the definition of hepatotoxicity in TB Rx?
Hepatotoxicity - ALT 3x upper limit normal w symptom, or 5x wihtout
57
What would you do if someone on TB Rx has hepatotoxicity?
Stop all drugs TB rechallenge once LFTs normalised: Restart every 3-5 days the first-line drugs, one by one with escalating doses, starting with least likely Ethambutol, then rifampicin, then isoniazid. If severe TB infection, treat with quinolone + injectable + 3rd drug in the mean time.
58
What are the side effects of isoniazid?
Hepatotoxicity Peripheral neuropathy (give vit B6 – pyridoxine) Hypersensitivity reaction: rash Lupus-like syndrome
59
What are the side effects of rifampicin?
Drug-drug interactions Mild hepatotoxicity Rash Bone marrow suppression, thrombocytopenia (red/organ urine – common, not adverse affect)
60
What are the side effects of PZA?
Most hepatotoxic Hyperuricaemia Arthralgia GI symptoms
61
What is the most worrying side effect of ethambutol?
Optic (retrobulbar) neuritis and neuropathy - loss of colour vision, blindness
62
What do you do if a patient gets a rash on TB Rx?
Rash - graded 1-4: Grade 4: SJ, TEN. Stop all drugs in rash grade 3-4, presence of consitutional symptoms.
63
What is the prevalence of MDR/XDR TB?
MDR: 3% of newly diagnosed cases, 18% if prev treated XDR: 7% of MDR TB is XDR
64
How do you test and treat for LTBI?
65
What are the risk factors for MDR TB?
- Previously Rx TB - Household contact with MDR TB
66
What are the genetic mutations for INH resistance?
katG: high level resistance inh2: low level resistance
67
What is the first line Rx for MDR-TB?
Shortest regimes BPALM - 6 months BPAL - 6 months BPaLM regimen (6 Bdq-Pa-Lzd-Mfx1 ): in patients with MDR/RR-TB where fluoroquinolone susceptibility is presumed or documented. This 6-month all-oral treatment regimen comprises bedaquiline, pretomanid, linezolid and moxifloxacin. Alternative: long individualised regime - Need at least 4 drugs that are effective 3 of class A (moxi/levo, bedaquiline, linezolid) plus one of class B - clofazamine, cycloserine, terizidine If cannot get 4 drugs from these classes, go to Class C: ethambutol, delamanid, imipenem, meropenem, amikacin, ethionamide, pyrainamide (try to not to give IV) How many drugs is up to you 18-20 months
68
How do you treat XDR TB?
XDR-TB regimen Admit to hospital At least 5 drugs, usually at least 7 drugs
69
How do you monitor response to Rx for MDR/XDR TB?
Monitoring of MDR-TB: Both monthly sputum smear microscopy and culture should be used
70
When do you start ARVs if co-infection with HIV diagnosed with TB MDR/XDR?
Immediately, within 2wks if CD4<50, or within 8wks absolute
71
How do you treat INH monoresistant TB?
Use rif + etb + pza + levofloxacin - 4 drugs for 6 months
72
How can you screen HIV patients for TB?
Screen all patients with 4 symptoms rule Use CRP >5 as a screen CXR may be used to screen Gene Xpert may be used to screen Inpatients with HIV with >10% TB prevalence in the area, test for TB with molecular test
73
Which HIV patients should be treated with IPT?
If HIV+ and no symptoms of TB, then give IPT unless contraindicated. 9 months if HIV positive INH 6 months for others
74
Which group of TB patients do you not treat immediately with ARVs if co diagnosis of TB/HIV?
TB meningitis- Delay ART >4wks if TB meningitis
75
What do you need to do if get a positive IGRA/TST?
If positive IGRA/TST – Remember to consider and rule out active TB infection - clinical and CXR before Rx for LTBI
76
What is interferon gamma release assays?
Test for LTBI. Measure IFN-gamma release by sensitised T cells after stimulation with MTB specific antigens (ESAT6, CFP10, TB7.7) quantiferon-TB gold, quanterferon gold plus, and T-SPOT.TB test
77
What are the benefits of IGRA over TST?
Zero cross-reactivity with BCG, and most NTM. Sensitivity equal to TST in individuals with culture-proven TB disease, but higher specificity No second clinic visit needed High reproducibility Clear negative in low risk patient indicates no further action
78
Difference between gene Xpert/Xpert Ultra/Xpert XDR?
Xpert and Ultra - both test for rifampicin resistance only XDR tests for resistance to Etoniamide, Ethambutol, Quinolone, amino glycoside, isoniazid
79
Biggest risk factor for TB transmission?
Inadequately treated MDR TB
80
Greatest risk factor for TB? Other risk factors?
HIV Malnutrition Diabetes, alcohol, smoking Indoor pollution
81
What is primary cutaneous TB?
Direct inoculation into skin from exogenous source - TB ulcer - TB chancre
82
Most common skin disease in TB?
Secondary
83
What is secondary cutaneous TB?
- Scrofuloderma - from direct extension of underling TB in lymph node / bone / joints - Acute haematogenous papules and pustules - Lupus vulgaris – multiple nodules and plaques on face and neck - TB gumma – multiple soft tissue abscess - Sinus tract
84
How to diagnose TB in secondary cutaenous TB?
AFB from skin lesion usually positive PPD also positive
85
Difference between tuberculid and secondary TB?
Tuberculid - Cutaenous hypersensitivity reactions (AFB not in lesion), PPD +ve
86
What does a sterilising drug do in TB?
defined as the ability of a drug to kill persistent and/or metabolically dormant organisms Shorten Rx and avoid relapse
87
Which is the most sterilising of the TB drugs?
Rifampicin 2nd: pyrazinamide
88
What is the main bactericidal drug in TB Rx?
Isoniazid
89
What is the role of ethambutol in TB?
Decreases resistance
90
When forming a TB regime, what are the key principles?
Need 2 bactericidal and 2 sterilising agents
91
When to start ARVs in TB meningitis/crypto meningitis?
4-6 weeks Definitely by 8 weeks
92
How long do you give steroids for in TB meningitis?
6 weeks then taper - total 8 weeks
93
What are the best tests for pulmonary TB?
Culture gold standard! Microscopy mandatory Molecular testing -LPA best BUT takes time and smear must be + -Gene xpert also good
94
Which TB drugs do liver toxicity?
Rifampicin Isoniazid Pyrazinamide Bedaquilline Pretonamid Ethionamide
95
Which drugs do ocular problems?
Ethambutol Linezolid
96
Which drugs cause rash?
Rifampicin Isoniazid Ethambutol
97
Isoniazid side effects?
Liver toxicity (Anytime) Rash/Hypersensitivity reaction Peripheral neuropathy Aplastic anaemia
98
Isoniazid side effects?
Liver toxicity (Anytime) Rash/Hypersensitivity reaction Peripheral neuropathy Sideroblastic anaemia
99
Rifampicin side effects?
Rash Hepatitis Bone marrow suppression Drug interactions
100
Pyrazinamide side effects?
Hepatits GI Arthralgia Hyperuricaemia
101
Ethambutol side effects?
Ocular - retinitis Rash
102
Linezolid side effects?
Peripheral neuropathy Bone marrow suppression (do not use for >6 months) GI Ocular
103
Moxi/levo SEs?
QTc prolongation Tendon rupture
104
Bedaquilline SEs?
QTc prolongation Liver toxicity Drug interactions HIV drugs
105
Pretonamid SEs?
Hepatic toxicity
106
Clofazamine SEs?
Skin pigmentation
107
Cycloserine SEs?
Psych SEs
108
What are the drugs in each class for TB?
109
Ethionamide SEs?
Thyroid dysfunction Liver dysfunction
110
Screening of HIV patients with TB?
Symptoms CRP CXR Molecular testing Adult and adolescent inpatients with HIV in medical wards where the TB prevalence is > 10% should be tested systematically for TB disease with a molecular WHO-recommended rapid diagnostic test
111
Treatment of MDR if cannot use BPAL and BPALM?
4 drugs Ideally 3 drugs from group A 18 months minimum no intensive phase if an aminoglycoside in not on the regimen
112
Treatment of TB in children?
Same as adults Weight based >25kg same doses as adults
113
What do you do to investigate HIV patients with suspected TB?
Molecular diagnosis Not LAMP - poor in HIV patients
114
Diagnosis of children with suspected TB? With symptoms?

Trop Med (49 decks)

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