TB Flashcards
What proportion of patients with HIV are TB +ve?
Around 25%
What proportion of TB is MDR/XR?
5%/0.5%
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What strategies can be employed to decrease the risk of TB transmission in hospital settings?
Open windows, high ceilings, UV light, NP95 masks
What is the risk of developing active TB from latent TB?
5-10%
Who should be tested for latent TB?
3 groups: Active TB contacts, current HIV immunosuppression, other high risk groups: endemic, homeless, healthworkers.
When is a TST positive?
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
Name 5 symptoms of pulmonary TB
Fever
Night sweats
Weight loss, anorexia
Fatigue
Cough with productive sputum
Haemoptysis seen in advanced disease
What % of TB is pulmonary?
80-85%
What are the most common sites of extrapulmonary TB?
Lymphadenitis
Pleural
Urogenital
Bone and joint disease
GI
CNS
Cutaneous
Pericardial
What proportion of TB is pulmonary/extra pulmonary in HIV patients?
Pulmonary 40%
EPTB 30-40%
Pulmonary + EPTB 20-30%
How does TB lymphadenitis present?
> 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)
What are the patterns of cutaneous TB disease?
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
How does secondary cutaenous TB present?
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
How may cutaenous tuberculids present?
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)
Where does musculoskeletal TB most often occur?
Thoracic spine (Lumbar = brucellosis)
Differentiate brucella in the spine vs TB
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
What is the most common presentation of urinary TB?
Aseptic pyuria
How can you diagnose genitourinary TB?
PPD >95% +ve
AFB in urine 80%
Culture >95%
How does TB meningitis present?
Meningitis with stupor and cranial nerve involvement is classic presentation
What is the CSF LP findings in TB?
Increase WCC (mononuclear - lymphocytic), low glucose, high protein
How can you definitively diagnose TB meningitis?
CSF AFB smear- sensitivity 10-30%
CSF-Xpert 60% sensitive
Xpert-CSF Centrifugated: 82% sensitive
Culture -66% sensitive
Also CXR, sputum AFB smear/culture
What is the WHO recommendation for testing for active TB?
All patients with cough >2wks should have TB screen with sputum x3 for AFB
What does ‘acid fast bacilli’ mean?
tubercle bacilli are identifiable from nearly all other species of bacteria by their ability to resist decolouration with weakly acidified alcohol
What types of gram stain are possible for TB?
Ziehl-Neelsen (ZN), fluorescence microscopy (auramine)
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%
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
Name the test and the organism?
TB, Ziehl Neelson stain
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
What is the gold standard for TB diagnosis?
Culture (detect as low as 100 AFB/ml), also provides DST
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
What is the organism? Which test? Why?
TB - ZN stain – cordons characteristic of MTB
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
What gene does Gene Xpert test for mutations in for rifampicin resistance?
rpoB gene
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%
How sensitive and specific is gene Xpert?
High sensitivity (98%) and specificity (99%), result in 2 hrs
What is urine LAM? In which group of patients is it useful in?
Lipoarabinomannan (LAM) - polysaccharide in mycobacterial cell wall
HIV positive
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
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
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
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)
What is the definition of TB monoresistance?
Resistance to a single drug
What is the definition of TB polyresistance?
Multiple drug resistance that does not constitute MDR/XDR
What is the definition of MDR TB?
Resistance to Rifampicin and Isoniazid (at least)
What is the definition of RR TB?
Rifampicin resistant TB. 90% of cases resistant to Rif will be resistant to INH
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
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)
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+
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
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)
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)
What is the definition of TB treatment failure as per WHO?
WHO define treatment failure as lack of conversion by 5 months
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
Who would you administer steroids to with TB Rx?
CNS TB
Pericardial TB
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
Which TB drugs cause hepatotoxicity?
Rifampicin - early
Isoniazid - anytime
Pyrazinamide - late (end of intensive phase)
What is the definition of hepatotoxicity in TB Rx?
Hepatotoxicity - ALT 3x upper limit normal w symptom, or 5x wihtout
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.
What are the side effects of isoniazid?
Hepatotoxicity
Peripheral neuropathy (give vit B6 – pyridoxine)
Hypersensitivity reaction: rash
Lupus-like syndrome
What are the side effects of rifampicin?
Drug-drug interactions
Mild hepatotoxicity
Rash
Bone marrow suppression, thrombocytopenia
(red/organ urine – common, not adverse affect)
What are the side effects of PZA?
Most hepatotoxic
Hyperuricaemia
Arthralgia
GI symptoms
What is the most worrying side effect of ethambutol?
Optic (retrobulbar) neuritis and neuropathy - loss of colour vision, blindness
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.
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
How do you test and treat for LTBI?
What are the risk factors for MDR TB?
- Previously Rx TB
- Household contact with MDR TB
What are the genetic mutations for INH resistance?
katG: high level resistance
inh2: low level resistance
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
How do you treat XDR TB?
XDR-TB regimen
Admit to hospital
At least 5 drugs, usually at least 7 drugs
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
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
How do you treat INH monoresistant TB?
Use rif + etb + pza + levofloxacin - 4 drugs for 6 months
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
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
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
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
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
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
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
Biggest risk factor for TB transmission?
Inadequately treated MDR TB
Greatest risk factor for TB? Other risk factors?
HIV
Malnutrition
Diabetes, alcohol, smoking
Indoor pollution
What is primary cutaneous TB?
Direct inoculation into skin from exogenous source
- TB ulcer
- TB chancre
Most common skin disease in TB?
Secondary
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
How to diagnose TB in secondary cutaenous TB?
AFB from skin lesion usually positive
PPD also positive
Difference between tuberculid and secondary TB?
Tuberculid - Cutaenous hypersensitivity reactions (AFB not in lesion), PPD +ve
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
Which is the most sterilising of the TB drugs?
Rifampicin
2nd: pyrazinamide
What is the main bactericidal drug in TB Rx?
Isoniazid
What is the role of ethambutol in TB?
Decreases resistance
When forming a TB regime, what are the key principles?
Need 2 bactericidal and 2 sterilising agents
When to start ARVs in TB meningitis/crypto meningitis?
4-6 weeks
Definitely by 8 weeks
How long do you give steroids for in TB meningitis?
6 weeks then taper - total 8 weeks
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
Which TB drugs do liver toxicity?
Rifampicin
Isoniazid
Pyrazinamide
Bedaquilline
Pretonamid
Ethionamide
Which drugs do ocular problems?
Ethambutol
Linezolid
Which drugs cause rash?
Rifampicin
Isoniazid
Ethambutol
Isoniazid side effects?
Liver toxicity (Anytime)
Rash/Hypersensitivity reaction
Peripheral neuropathy
Aplastic anaemia
Isoniazid side effects?
Liver toxicity (Anytime)
Rash/Hypersensitivity reaction
Peripheral neuropathy
Sideroblastic anaemia
Rifampicin side effects?
Rash
Hepatitis
Bone marrow suppression
Drug interactions
Pyrazinamide side effects?
Hepatits
GI
Arthralgia
Hyperuricaemia
Ethambutol side effects?
Ocular - retinitis
Rash
Linezolid side effects?
Peripheral neuropathy
Bone marrow suppression (do not use for >6 months)
GI
Ocular
Moxi/levo SEs?
QTc prolongation
Tendon rupture
Bedaquilline SEs?
QTc prolongation
Liver toxicity
Drug interactions HIV drugs
Pretonamid SEs?
Hepatic toxicity
Clofazamine SEs?
Skin pigmentation
Cycloserine SEs?
Psych SEs
What are the drugs in each class for TB?
Ethionamide SEs?
Thyroid dysfunction
Liver dysfunction
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
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
Treatment of TB in children?
Same as adults
Weight based
>25kg same doses as adults
What do you do to investigate HIV patients with suspected TB?
Molecular diagnosis
Not LAMP - poor in HIV patients
Diagnosis of children with suspected TB? With symptoms?
