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Ryan Tee Heng Seong

on 13 October 2014

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Transcript of Tuberculosis

Imaging + laboratory tests
AFB smears or cultures
All suspected patients should submit at least 2 sputum samples (preferably in morning)
If unable to produce sputum, sputum induction should be performed (nebulised hypertonic saline, BAL or gastric lavage)
However, sputum culture is time consuming; NAAT can be used for rapid diagnosis of TB if available
TB high risk groups
Close contacts (household)
Immunocompromised (HIV, prednisolone >10g/day, TNF-a inhibitor)
Post-organ transplant
Substance abusers
Crowded conditions (prison, homelessness)

Extrapulmonary TB
Tuberculous lymphadenitis
FNA, excisional biopsy is only done if FNA cannot be made

Pleural TB
thoracocentensis under US guifance
staining is not useful;
ADA is quite sensitive and specific
Lymphocytosis, low glucose and high protein

Tuberculous meningitis
ADA can also be used in CSF analysis
CT and MRI for imaging
Pulmonary and laryngeal forms : infectious
Non-pulmonary forms : not infectious
Infectiveness (+) when multiple cavities are shown in CXR

Two phases
Intensive phase (2 months)
Maintenance phase (6 months)
Latent TB
Positive tuberculin skin test
Normal CXR findings
Positive smear/culture

TST test can be falsely positive in patients with previous BCG vaccination
"Booster phenomenon"
TB in children and pregnancy
Adverse drug effects
Management of Tuberculosis
Tuberculin skin test (Mantoux test)
Different diameter of indurations to different populations
Household contact
HIV, prednisolone > 10mg/day
Post organ transplant
Prior TB as seen on CXR
> 10 mm
Immigration from high risk countries
Crowded conditions
Lab personnels
DM, ESRF, lymphoma, silicosis
> 5mm
> 15 mm
No risk factor populations
Rapid results in 1-2 days
PPV of > 85% in AFB smear positive specimens
Can also detect MTB in 50-80% of AFB smear negative patients
Fluorescence Microscopy
Conventional lacks sensivitity
LED FM is better and should be used
Serological Assay
Cross reactivity rate to BCG and NTB is high, so is not preferred to be used as test for diagnosis
Imaging in PTB
Consolidation and cavitation are hallmarks
Any abnormalities should be suspected
15% of primary TB can have NORMAL imaging

HRCT has better sensitivity and specificity
Tx of new cases
2 months of EHRZ + 4 months of HR

Rifampin should be used for the whole duration (unfavourable outcomes are higher in regimens w/o rifampin)

If Ethambutol is c/i, streptomycin can be used
Previously tx cases
Tx for >1 month and now smear/culture positive (failure or relapse)
MDR-TB is the concern here
Drug sensitivity must be done
Intensive phase :
< 2 weeks, restart from day 1
> 2 weeks, continue for the last dose
Maintenance phase
> 80% of total dose and smear positive, can be stopped
> 80% of total dose and smear positive, continue
< 80% total dose and
> 2 months interruption
, restart from beginning
< 80% total dose and
< 2 months interruption
, start from the date it stops
Optimal Duration of Treatment
For pulmonary TB, at least 6 months of treatment
Extra-pulmonary TB
WHO recommendations:
Meningeal : 9-
months, streptomycin instead of ethambutol
Bone and joint : 6-

Others : min of 6 months
Miliary : not sure
Role of Steroids
Corticosteroids should be used in TB meningitis or pericarditis

Prednisolone and Mycobacterium indicus pranii in Tuberculous Pericarditis. Bongani M. Mayosi et al.
N Engl J Med 2014; September 18, 2014
Prednisolone does not decrease mortality but it does reduce incidence of constrictive pericarditis
Only give to high risk groups ( large pericardial effusion and high inflammatory markers )
Steroids may have reduced effect in HIV as there is less inflammatory response
Booster phenomenon

Negative TST in a previously infected patient
"Amnesia" of memory T cells
2 steps TST test is done. 2nd test is done after 1-3 weeks later
1st and 2nd negative : uninfected
1st negative but 2nd positive :
"Booster phenonemon"
IF Gamma Release Assay
Detect the IF-gamma produced during MTB infection
Higher spec and PPV
Avoid false positive in BCG vaccination or past NTM infection

Treatment of LTBI
INH for 9 months
Shorter course of six months is an acceptable alternative
Beware of Vitamin B6 deficiency
TB in children
Most of sputum negative
Strongest RF : contact with TB (+) person
Dx : TST, CXR and sputum examination
Tx : same as adult except for the doses
INH can cause refractory status epilepticus in a child; pyridoxine should be added if it is given
Risk of active TB (+) before adolescence, LTBI is a major risk

TST is the test of choice
IGRA is less likely to be positive in < 2 years old
Amount of IFN-gamma released is correlated directly to the age
Sensitivity of IGRA and TST reduces in younger children

Tx : 6 months of INH ( WHO & NICE) or 3 mths of INH + Rifampicin ( NICE ); applies to HIV infected children as well
Congenital and Perinatal TB
Distinction between congenital or postnatal acquired TB has litle significance
Consider in pneumonia/sepsis unresponsive to standard treatment

Who needs standard prophylaxis
Every baby born to mother with active PTB
except those dx > 2 months before delivery + smear negative

Prophylaxis :
6 months of INH / 3 months of INH + rifampin followed by BCG
Pregnancy and Lactation
All except streptomycin are safe in pregnancy and breastfeeding
Pyridoxine 25 mg/day should be given to prevent foetal neurotoxicity

OCP : rifampicin is a P450 inducer; so it may reduce the efficacy of OCP. Patient should be advised to use an alternative method of contraception

Liver impairment
Always take a baseline LFT
Regular monitoring every 2 weeks for the first 2 months should be done
If liver enzymes are 3X > ULN before initiation, different regimens should be considered (with fewer hepatotoxic drugs)
All anti-TB drugs are hepatotoxic except ethambutol, streptomycin and FQ
( INH and pyrazinamide MOST toxic )
Renal Impairment
Preferred regimen is the same as in normal renal function but at a different frequencies (3 times per week instead of daily)
Pyrizinamide and ethambutol are renally excreted
All 4 drugs can be given after hemodialysis
Avoid streptomycin if possible
Rule out TB especially in patient with CD4 < 200
EPTB lesions are commonly found in HIV ( lymphatic, meningeal and disseminated TB)
Look out for 4 symptoms in TB : fever, cough, night sweats and LOW (absence of 4 symptoms have high NPV)

Dx : same as in HIV negative patients
Sputum smears negative in 50% ( lower AFB density in sputum with decreasing CD4)
IGRA has only 60% sens and spec in HIV positive patients
Normal CXR in about 20% with less cavitations
Hence, we always need a culture for diagnosis
Daily regimen of EHRZ for intensive phase
Minimum of 6 months
EPTB : an be extended to 9-12 months
TB is associated with high risk of IRIS, hence the question of " when to restart HAART"

SAPIT & CAMELIA trials : CD<50, more IRIS in early HAART but the overall survival benefit > adverse events; hence the recommendation
CD4 < 50 : restart in 2 weeks; watch out for IRIS
CD4 > 50 : restart in 2 months

Caveat in tuberculous meningitis : no survival benefit in early HAART
DDI concerns
Rifampin : CYP P450 inducers
Interactions with all PIs (increase metabolism and decrease efficacy), hence not recommended
Also reduce the level of NVP

In such cases, rifabutin should be used as it has lesser effect on drugs metabolism
With symptoms + AST/ALT > 3X UNL or
Without symptoms + AST/ALT > 5X UNL

What to do?
Less AFB burden : can stop
High AFB burden : Use SEF (least hepatotoxic regimen) for 18-24 months; moxifloxacin and levofloxacin preferred
Note that Ritonavir inhibits CYP 3A4 but induces CYP 1A2 and 2C19; often used with Lopinavir to boost its concentration
Our CPG also states that if CD4 > 350 consider HAART ONLY if it drops below 350
Overlapping Toxicities
Peripheral neuropathy :
DDI & d4T
Hepatototixity :
Almost all anti-TB drugs
GI disturbances : all
Bone marrow suppression :
Skin rash :
INH, Rifampin, pyrazinamide
Normally within 3 months of TB treatment
Paradoxical worsening of symptoms (fever, lymphadenitis)
Most significant RF : EPTB
Tx : 4 weeks prednisolone
Extra point :
CTX reduces all course mortality in TB-HIV in a RCT. So should be started ASAP and throughout TB tx
Follow Up
Follow up in 1st, 2nd, 4th and 6th month
2nd and 6th month (end of intensive and maintenance tx) :
repeat sputum smear if initial smear positive
If initial smear negative, repeat sputum smear at 2nd month
If still negative, no further sample should be taken
A positive sputum smear at 2nd month : referral to specialist
Sputum culture and sensitivity should be taken at the start of anti-TB tx
Drugs adverse effects
INH : transaminitis, vitamin B6 deficiency, peripheral neuropathy
Rifampin : bone marrow suppression
Ethambutol : eye (red-green colour blindness), hyperuricemia
Pyrazinamide : hyperuricemia
INH and rifampicin are also associated with drug induced rashes. Desensitization maybe needed

Pyrazinamide and INH are the most hepatotoxic drugs

Ethambutol and pyrazinamide can cause acute gouty flare, but if no flares do not discontinue
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