by

Dr. Mohd Daud Che Yusof

FMS
KK Beserah

1
 OBJECTIVES OF CPG
• Making evidence-based decisions
• Appropriate management of TB on:
– screening
– diagnosis
– treatment
– follow-up
– prevention
– referral

2
 SCOPE OF CPG
• High Risk Groups
• Investigations
• Treatment of TB in Adults
• LTBI in Adults
• TB in Pregnancy, Lactation & Use of Oral Contraceptive Pills
• Follow-up & Adverse Drug Events
• Referral Criteria

3
 HIGH RISK GROUPS

• Close TB contacts 
• Immunocompromised patients:
– Diabetes mellitus
– HIV
– Chronic obstructive pulmonary disease
– End-stage renal disease
– Malignancy
– Malnutrition
• Substance abusers & cigarette smokers
• Poor people living in overcrowded conditions
4
 HIGH RISK GROUPS

• Immigrant population

– Tuberculin skin test (TST) was used to screen for latent TB infection
and a higher positive rate of TST was found in foreign compared to
local patients
– highly mobile within the country as well as across borders, and who
do not undergo any health screening
– Foreign patients were more significantly associated with non-
compliance to anti-tubercular therapy

5
 TB –
LABORATORY
INVESTIGATIONS

6
 INTRODUCTION
• Diagnosis of TB is based on

– the detection of acid fast bacilli (AFB) on

smears &

– culture of Mycobacterium tuberculosis from

clinical specimens.

7
• Specimen collection

• Lab investigations
– Microscopy
– Culture
– Identification
– AntiTB sensitivity
– Molecular
8
 SPUTUM COLLECTION
• Sputum1
• At least 2 specimens
• At least one early morning specimen

• For patients who are unable to spontaneously

expectorate adequate sputum specimens
• Sputum induction with nebulised hypertonic saline
• Fiberoptic bronchoscopy with bronchoalveolar lavage
• Gastric lavage especially in paediatric group
(neutralise with sodium bicarbonate)
WHO, 2010
1

9
 OTHER SAMPLES
• Sterile body fluids
• include blood, CSF, pleural fluid, peritoneal
fluid
• should be collected aseptically
• transported immediately to laboratory in
sterile container

10
 MICROSCOPY
• Microscopy
• Presumptive diagnosis
• Sputum
• Ziehl-Neelsen staining for AFB
• Conventional microscope
• low sensitivity (20 - 60%)1
• Light emitting diode-based
fluorescence microscopy (LED FM)2
• 10% more sensitive
• shorter time spent
• quicker turnaround time
1 Steingart KR et al., Lancet Infect Dis, 2006
2 Shenai S et al., Int J Tuberc Lung Dis, 2011

11
CONVENTIONAL LIGHT MICROSCOPY

Acid fast bailli

IMMUNOFLUORESCENCE MICROSCOPY

AFB bacilli – IF stain (low mycobacterial load)

 CULTURE & SENSITIVITY

• Culture
• conventional method using LJ or Ogawa
• 6 - 8 weeks

• Drug-susceptibility testing
• 1 - 2 months

14
 PHENOTYPIC METHOD –
Proportion method

A B

M. tuberculosis Susceptible
to INH

Without drug With drug - INH

Conventional culture medium (solid) –
TB. Rough, buff, cream-coloured
colonies, compact, corded colonies
 CULTURE & SENSITIVITY

• Liquid culture media

a. Bactec MGIT
- detection by 2 weeks
- identification within 3 weeks
- sensitivity testing by 4 weeks
b. Bactec MycoF only for blood sample

17
 NUCLEIC ACID
AMPLIFICATION TEST (NAAT)
• NAAT
• molecular technique
• provide rapid results within 24 - 48 hours
• ability to confirm presence of Mycobacterium in 50
- 80% AFB smear negative & culture positive1,2
• detect Mycobacterium in specimens weeks earlier
than culture for 80 - 90% patients2

CDC, MMWR Morb Mortal Wkly Rep, 2009

1

2Sarmiento OL et al., J Clin Microbiol, 2003

18
 LINE PROBE ASSAY (LPA)

• Line Probe Assay (LPA)

• detect rifampicin & isoniazid resistance in
smear positive sputum or culture isolates
• carried out in a TB risk level 2 laboratory

19
 GENE XPERT MTB

• Gene Xpert MTB

• for detection of rifampicin resistance Mycobacterium
• fast & accurate
• can be used in peripheral laboratories
• fully automated, near the patient, uses a robust system &
technically simple

20
22
 TAKE HOME MESSAGES

• LED FM has more advantages than

conventional microscopy

• NAAT e.g. LPA is able to shorten the turn-

around time for identification & antiTB testing

23
IMAGING IN TB
 INTRODUCTION

 There are NO imaging features that are

pathognomonic for TB & the findings may
mimic those of many other diseases.
 iMAGING MODALITIES IN PTB
CXR is the most widely available imaging modality &
should be the first line of investigation for both
symptomatic cases & high risk contacts (screening).

CT is more technically challenging & is not as readily

available, but is useful in the assessment of PTB
complications.

MRI maybe used in special circumstances, but is

more expensive & is of limited availability.
 TUBERCULOSIS
PATHOGENESIS
 1st stage – infection by M. tubeculosis is a
subclinical event, contained by the body defenses
in approx. 90 - 95%. In the remaining 5 - 10% the
disease may manifest sometime during their
lifetime i.e. latent TB.

 2nd stage – clinically manifested TB

 NEW CONCEPT

Radiographic appearance may depend on the

integrity of the host immune response

Severely immunocompromised patients show a

tendency to have radiological features of
primary TB

Immunocompetent patients tend to have

radiological features of post-primary TB
IMAGING FEATURES ON CXR
Primary TB
parenchymal disease – homogenous consolidation
lymphadenopathy
miliary disease
pleural effusion

Post-primary TB
parenchymal disease – patchy consolidation
cavitation
airway involvement
pleural extension
Normal Chest X-ray
 CHEST RADIOGRAPH
Normal chest radiography may be seen in up to 15% of
patients with proven TB.1

CXR is sensitive but not specific; any abnormality may

suggest TB in an immunosuppressed person.

Abnormalities on chest radiographs may be suggestive of,

but never diagnostic of, TB.

Activity of TB cannot be made accurately on a single

radiograph alone, sputum smears/culture must be obtained.

Burrill J et al. Radiographics, 2007

1
 GRADING OF PTB SEVERITY
FROM CXR
 Minimal
 Slight lesions with NO cavity.
 Confined to small parts of one or both lungs.
 Total extent of lesion not exceeding the upper zone.
 Moderate
 Dense confluent lesions not exceeding one third of one lung

OR
 disseminated slight to moderate density in one or both lungs not
exceeding the volume of one lung.
 Total diameter of cavity should not exceed 4 cm.
 Advanced
 Lesions are more extensive than moderately advanced.
 HIGH RESOLUTION COMPUTERISED
TOMOGRAPHY (HRCT)
It is more sensitive than CXR in the detection &
characterization of subtle, localized and disseminated
parenchymal disease & mediastinal lymphadenopathy.

CT is useful in determining disease activity.

CT is helpful in the evaluation of pleural complication

(effusion, empyema, bronchopleural fistula) not
evident on CXR.

Management of MDR-TB
TREE-IN-BUD APPEARANCE
 RECOMMENDATION 8
 Chest radiography should be used as the primary
imaging modality to aid diagnosis & management
of pulmonary & extrapulmonary TB. (Grade C)

 Computerised tomography maybe considered in

cases of normal chest radiography but with high
clinical suspicion or in the management of
complication of pulmonary TB. (Grade C)
TREATMENT of TB
in ADULTS

47
 AIM OF TREATMENT
• Cure & reduce transmission

• Risk of developing TB is determined:

– infectiousness of index case
– smear positive PTB; PTB with cavities; laryngeal TB
– nature & duration of contact
– immune status of contact

48
 EDUCATION
a. Nature of disease
b. Necessity of strict adherence with prolonged
treatment
c. Risks of defaulting treatment
d. Side effects of medication
e. Risks of transmission & need for respiratory
hygiene as well as cough/sneeze etiquette

49
PULMONARY TUBERCULOSIS (PTB)
IN ADULTS
 NEW CASES
• 6-month regimen consisting of 2 months of
EHRZ (2EHRZ) followed by 4 months of HR
(4HR) is recommended for newly-diagnosed
PTB.

51
 RECOMMENDED ANTITB DRUGS

RECOMMENDED DOSES
Daily 3X a week
DRUG
Dose (range) Maximum in Dose (range) Maximum in
in mg/kg mg in mg/kg mg
body weight body weight

Isoniazid (H) 5 (4 - 6) 300 10 (8 - 12) 900

Rifampicin (R) 10 (8 - 12) 600 10 (8 - 12) 600
Pyrazinamide 25 (20 - 30) 2000 35 (30 – 40)* 3000*
(Z)
Ethambutol 15 (15 - 20) 1600 30 (25 – 35)* 2400*
(E)
Streptomycin 15 (12 - 18) 1000 15 (12 – 18)* 1500*
(S) 52
 NEW CASES (cont.)
• Pyridoxine 10 - 50 mg daily needs to be added
if isoniazid is prescribed.
• *Daily treatment is the preferred regimen.
Adopted from WHO. Treatment of Tuberculosis Guidelines (4th Ed.), 2010

53
 IMPORTANT POINTS
• Rifampicin
– should be used for the whole duration of treatment.
– NS difference in effectiveness & safety between rifampicin
& other antibiotics in the rifamycin group.
– whenever possible, rifampicin dosage should not be lower
than recommended dosage (10 - 12 mg/kg).
• Pyrazinamide beyond 2 months during the intensive
phase does not confer further advantage if the
organism is fully susceptible.
• Recurrence rate is low for both ethambutol-based
regimen & for streptomycin-based regimen.
54
TREATMENT OF NEW CASES

55
 PREVIOUSLY TREATED TB
• New cases who have taken treatment for
more than one month & are currently smear
or culture positive again (i.e. failure, relapse or
return after default)

56
 DEFINITION
Previously treated Patient previously treated for TB including
relapse, failure & default cases .
Relapse A patient whose most recent treatment
outcome was “cured” or “treatment
completed”, & who is subsequently
diagnosed with bacteriologically positive TB
by sputum smear microscopy or culture.
Treatment after A patient who has received Category I
failure treatment for TB & in whom treatment has
failed.
Treatment after A patient who returns to treatment,
default bacteriologically positive by sputum smear
microscopy or culture, following
interruption of treatment for 2 or more
consecutive months. 57
 PREVIOUSLY TREATED TB
• Recommend: retreatment regimen containing first-
line drugs 2HRZES/1HRZE/5HRE if country-specific
data show low or medium levels of MDR-TB in these
patients or if such data is not available.

• Drug sensitivity test (DST) must be done for patients.

When results become available, drug regimen should
be adjusted appropriately.

*This is WHO statement, no retrievable evidence

available.
58
 TO START OR NOT?
• Interruption in intensive phase:
– If ≥14 days, to restart from beginning i.e. Day 1.
– If <14 days, to continue form last dose.

59
 TO START OR NOT?
• Interruption in maintenance phase:
– If interruption occurs after patient receives 80% of total
planned doses, treatment may be stopped if sputum AFB
smear was negative at initial presentation. If sputum AFB
smear was positive, treatment should be continued to
achieve total number of doses.
– If total doses <80% & interruption lapse is ≥2 months,
restart treatment from beginning.
– If total doses is <80% & interruption lapse is <2 months,
continue treatment from date it stops to complete full
course.

60
 TREATMENT OF
PREVIOUSLY TREATED TB

61
 OPTIMAL DURATION
• Patients with sputum positive PTB should receive
antiTB drugs for a minimum duration of 6 months.

• Regimens with shorter duration of rifampicin are

associated with higher risk of failure, relapse &
acquired drug resistance.

• Even in patients with non-cavitary disease &

confirmed sputum culture, conversion at 2 months
fares poorer with a 4-month regimen compared to 6-
month regimen.
62
OPTIMAL DURATION

63
 MAINTENANCE PHASE
• In new patients with PTB, WHO recommends daily
dosing throughout the course of antiTB treatment.

• However, a daily intensive phase followed by thrice

weekly maintenance phase is an option provided
that each dose is directly observed & patient has
improved clinically.

• A maintenance phase with twice weekly dosing is not

recommended.

64
 MAINTENANCE PHASE
• There is no difference in treatment failure, relapse &
acquired drug resistance rates between daily &
different intermittent dosing regimens in the
maintenance phase.1, 2, 3
Menzies D et al., PLoS Med, 2009
1

Mwandumba HC et al., Cochrane, 2001

2

3Chang KC et al., Thorax, 2011

65
MAINTENANCE PHASE

66
 FIXED-DOSE COMBINATION
(FDC) IN MALAYSIA
• Forecox-Trac Film Coated Tab: isoniazid, rifampicin,
ethambutol & pyrazinamide
• Rimactazid 300 Sugar Coated Tab: isoniazid, & rifampicin
• Rimcure 3-FDC Film Coated Tab: isoniazid, rifampicin &
pyrazinamide
• Akurit-Z Tab: isoniazid, rifampin (rifampicin) & pyrazinamide
• Akurit Tab: isoniazid & rifampin (rifampicin)
• Akurit-Z Kid Dispersible Tab: isoniazid, rifampin (rifampicin) &
pyrazinamide
• Akurit-4: ethambutol, isoniazid, rifampin (rifampicin) &
pyrazinamide

67
 FDC IN MOH
• 4-Drug combination: isoniazid 75 mg,
rifampicin 150 mg, pyrazinamide 400 mg &
ethambutol 275 mg tablet

• 2-Drug combination: isoniazid 75 mg &

rifampicin 150 mg

68
 RECOMMENDED DOSES
• 30 - 37 kg body weight: 2 tablets daily

• 38 - 54 kg body weight: 3 tablets daily

• 55 - 70 kg body weight: 4 tablets daily

• More than 70 kg body weight: 5 tablets daily

69
 EFFECTIVENESS
• FDCs compared to separate-drug regimens
significantly reduce risk of non-compliance by
17% & consequently improve effectiveness of
therapy.1

• In term of bioavailability, FDCs are proven to

be bioequivalent to separate-drugs
formulations at the same dose levels.2
Bangalore S et al., Am J Med, 2007
1

2Agrawal S et al., Int J Pharm, 2002

70
 OTHER ADVANTAGES
• Smaller number of tablets to be ingested may
also encourage patient adherence.

• Prescription errors are likely to be less

frequent for FDCs due to easy adjustment of
dosage according to patient weight.

71
FDC

72
 DIRECTLY OBSERVED
THERAPY (DOT)
• Direct observation of drug ingestion of the
DOTS component should not be the sole
emphasis in TB control programmes.

• It should not be a blanket approach; instead it

should be a process of negotiation & support,
incorporating patients’ characteristics &
choices.

73
 DIRECTLY OBSERVED
THERAPY (DOT)
• Enhanced DOTS involving intensive contact
tracing & treating the contacts with TB can
reduce incidence of TB within a community
(p=0.04).1
1 Cavalcante SC et al., Int J Tuberc & Lung Dis. 2010

74
DOT

75
EXTRAPULMONARY TUBERCULOSIS
(EPTB) IN ADULTS
 DURATION OF EPTB TREATMENT -
NICE RECOMMENDATION1
• Meningeal TB – 2 months S/EHRZ+10HR*
• Peripheral lymph node TB – should normally
be stopped after 6 months
• Bone & joint TB – 6 months
• Pericardial TB – 6 months
1 National Collaborating Centre for Chronic Conditions and the Centre for Clinical Practice. Tuberculosis: clinical diagnosis and
management of tuberculosis, and measures for its prevention and control. 2011

77
 DURATION OF EPTB TREATMENT
- WHO RECOMMENDATION1
• Regimen should contain 6 months of
rifampicin: 2HRZE/4HR*
• Duration of treatment for TB meningitis is 9 -
12 months &, bone & joint TB is 9 months
1 World Health Organization. Treatment of tuberculosis Guidelines. Fourth ed. 2010

78
 MILIARY & DISSEMINATED TB

• There is no retrievable evidence on optimal

duration of treatment for disseminated TB &
miliary TB.

• There should be low threshold to suspect TB

meningitis in these groups of patients &
treatment duration should be prolonged
between 9 to 12 months.

79
OPTIMAL DURATION OF
EPTB TREATMENT

80
 CORTICOSTEROIDS IN EPTB

• Corticosteroid therapy may benefit patients

with some forms of EPTB. However literature
on corticosteroids in various form of EPTB is
scant.

81
CORTICOSTEROIDS IN
EPTB TREATMENT

82
 SURGERY IN PTB
• Diagnosis & obtaining tissue for culture & drug
sensitivity

• Management of TB complications

• Treatment of the disease itself where drug

therapy alone may be deemed insufficient to
achieve cure

83
 TAKE HOME MESSAGES
• Adhere to standard regime

• Use correct doses & adequate duration

• Ensure compliance

• Treatment needs to be individualised

• Consult a doctor/physician with experience in

TB management when in doubt
84
 TB –
CONTACT TRACING
 Contact
Contact Tracing
Tracing
Site
Site of
of disease
disease
Pulmonary
Pulmonary//Laryngeal
Laryngeal// Extrapulmonary
Extrapulmonary
Pleural
Pleural

Contact
Contacttracing
tracingisis
Sputum
SputumAFB
AFB Sputum
SputumAFB INDICATED
AFB INDICATEDto tofind
find
smear
smear(+ve)
(+ve) smear
smear(-ve) primary
(-ve) primarysource
source

Contact
Contacttracing
tracing Cavitary
Cavitary Non-cavitary
Non-cavitary
should
shouldbe
beDONE
DONE disease
disease disease
disease

Contact
Contacttracing
tracingshould
should Contact
Contacttracing
tracingshould
should
be
beCONSIDERED
CONSIDERED be
beCONSIDERED
CONSIDEREDifif
sufficient
sufficientresources
resources 86
 Investigations
Investigations for
for Contact
Contact Tracing
Tracing in
in Adults
Adults
PTB
PTBclose
closecontact*
contact*

Symptomatic
Symptomatic Asymptomatic
Asymptomatic

Evaluate
Evaluatefor
foractive
activeTB: Mantoux
TB: MantouxTest
Test
••CXR
CXR
••Sputum
SputumAFB
AFB
••Mantoux
MantouxTest
Test
>>10
10mm
mm <10
<10mm
mm

Diagnosis
Diagnosisconfirmed:
confirmed: CXR
CXR Discharge
Discharge
TREAT
TREAT with
withadvice**
advice**
Diagnosis
Diagnosisinconclusive:
inconclusive:
REFER
REFERSpecialist Abnormal Normal:
Specialist Abnormal Normal:Manage
Manage
as
asLTBI
LTBI
87
Investigations
Investigations for
for Contact
Contact Tracing
Tracing in
in Adults
Adults

*Immunocompetent close contacts.

**To seek medical advice if patient has
symptoms suggestive of TB such as fever,
cough, etc. for more than 2 weeks.

88
 Children
Childrenwith
withPositive
PositiveHistory
Historyof
ofContact
Contactwith
withTB
TB
Mantoux
MantouxTest
Test
>>10
10mm
mm <10
<10mm
mm
CXR
CXR Symptomatic Asymptomatic
Symptomatic Asymptomatic
Normal
Normal Abnormal
Abnormal CXR
CXR Check
CheckBCG
BCG

Symptoms
Symptoms
suggest
suggestTB
TB Normal
Normal Abnormal
Abnormal NO
NOscar
scar Scar
Scar
Asymptomatic
Asymptomatic

>>55y.o.
y.o. <5
<5y.o.
y.o.

F/U
F/U
Treat
Treatas
asLTBI
LTBI Refer
ReferPaed
Paed IxIx Refer
ReferPaed.
Paed. BCG
BCG F/U
F/U
89
LATENT TB IN ADULTS 

by
Assoc. Prof. Pang Yong Kek

90
 LTBI
LTBI is diagnosed when an individual:

– shows positive reaction to the TST/IGRA

but

– does not have any clinical, bacteriological (if

done), or radiographic evidence of active TB

Interferon Gamma Release Assay

91
 DIAGNOSTIC CRITERIA
• No symptoms to suggest active disease

• Normal CXR (usually)

• Negative sputum smear for AFB (if collected)

• “Positive” TST (Mantoux Test)/IGRA

92
 DIAGNOSTIC CRITERIA
If the CXR is abnormal,

•ensure no changes are seen on repeat CXR (≥ 6

months apart)

•repeat sputum induction or BAL for AFB smear

& culture should be considered, even if no
changes are seen on repeat CXR

93
 DIAGNOSTIC CRITERIA
Remark:

•Calcified nodular lesions (calcified granulomas)

& apical or basal pleural thickening pose a
lower risk for future progression to active TB

→ Hence, does not require treatment

94
WHY TREATMENT OF LTBI IS
NECESSARY?

95
 TB CONTROL PROGRAMME
• We know that:
• early detection & prompt treatment of
active TB (esp. infectious TB), constitute one
of the most important strategies to control
TB

96
 UNIQUE FEATURES OF TB
– However, the signs & symptoms of active TB, are
usually quite subtle in early stage.

– Consequently, it will not alert the victims to seek

early medical attention.

– The lack of florid symptoms & signs often elude

early detection by the health care providers.

97
SO, WHY BOTHER?

98
 TREATMENT OF LTBI
– When LTBI reactivated, it will spread the disease in
the community.

– LTBI Rx prevents this sporadic reactivation &

dissemination of TB.  

• Thus, it is certainly an essential component of

TB control in the community. 

99
100
• Dependent on the
demonstration of
host immune
response toward
tuberculous
proteins.

101
 TUBERCULIN SKIN TEST (TST)

• However, interpretation of TST posts a big

challenge to the healthcare professionals.

102
 THE SHORTCOMINGS OF TST

Tuberculin contains
>200 proteins, widely
shared among the
mycobacteria.

103
 THE SHORTCOMINGS OF TST
• Due to this cross-reactivity, it has a poor specificity in
population which have been extensively vaccinated
with BCG.  

• Furthermore, NTM infection is relatively common in

tropical countries - further compound the diagnosis.

104
 NEW TESTS - IGRA
• Recently, with the invention of 2 new tests,
collectively known as IGRA
• QuantiFERON-Gold-In-Tube (QFT-GIT) test
• Elispot test (T-SPOT)
 the prospect of differentiating LTBI from BCG
vaccination/NTM infection has becoming promising.  

105
 SENSITIVITY & SPECIFICITY
OF IGRA

– Although this test is more specific, it still

cannot overcome the limitation that

• the test result is dependent on the immune

status of the tested individuals

106
 WHO SHOULD BE TESTED?

• Only individuals who are at high risk of

acquiring LTBI or developing TB reactivation
should be investigated.

• Treatment might be considered for those who

are positive for LTBI.

108
 POSITIVE TST FOR LTBI

Positive TST Type of Individuals

(Measurement)
≥5 mm • HIV-infected persons

• Organ transplant recipients

• Persons who are immunosuppressed for

other reasons (such as those taking the
equivalent of >15 mg/day of prednisolone
for ≥1 month or taking TNF-α
antagonists)

109
 POSITIVE TST FOR LTBI
Positive TST Type of Individuals
(Measurement)
≥10 mm • Close contacts

• Recent immigrants (< 2 years)

• Injecting drug users

• Residents & employees of high risk

congregate settings(such as correctional
facilities, nursing homes, homeless
shelters, hospitals & other healthcare
facilities)

• Persons with fibrotic changes on CXR 110

 POSITIVE TST FOR LTBI

Positive TST Type of Individuals

(Measurement)
≥15 mm • Individuals from countries with low
incidence of TB

111
 WHO SHOULD BE TESTED?
• The goal of testing – to identify persons who are
going to benefit most from treatment.

• A pre-test evaluation should be made to identify

these individuals.

• There are two broad categories of individuals

1. Persons who have recent close contact
2. Immunocompromised individuals

112
 WHO ELSE SHOULD BE SCREENED?

1. Individuals who are at increased risk of acquiring TB

infection (e.g. prison-warden, nursing home
residents/workers, intravenous drug users &
healthcare workers)

2. Immunocompromised individuals who are at

increased risk of reactivation (e.g. HIV infection,
patients on immunosuppresants, patients with
advanced organ failure)

113
 ALGORITHM FOR SCREENING &
TREATMENT

Target individuals - screen for symptoms of

active TB
• If active TB suspected - CXR & sputum
direct smear & Mantoux test

• If otherwise – TST (Mantoux test)

• TST <5 mm – no further test
• TST ≥5 mm, may proceed with IGRA test

114
PROPOSED ALGORITHM
OF SCREENING &
TREATMENT OF LTBI

115
SHORTCOMING OF THIS ALGORITHM

• Lack of longitudinal study that treatment of

LTBI using TST/IGRA is effective in preventing
disease reactivation in high burden countries.
– A study of this nature is desperately required.

116
WHAT IS THE ADVANTAGE OF
TARGETED SCREENING?

Active
TB

Latent
TB

117
THE OCCULT TARGETS ARE FLAGGED!

118
 ADVANTAGES OF TARGETED CONTACT
SCREENING
1. A positive TST is more likely to indicate LTBI - less
false positive result.

2. They are likely to benefit most from the treatment -

reactivation risk is higher in recent contact.

3. Besides, they may be more likely to accept therapy &

adhere to it. 

119
 ANTITB REGIMENS FOR LTBI

Drugs Duration Interval Completion criteria

Isoniazid 6-9 Daily  180 doses in 9 months (6-

months month regimen)
 270 doses in 12 months (9-
month regimen)

Isoniazid + 4 months Daily  120 doses within 6 months

rifampicin
Rifampicin 4 months Daily  120 doses within 6 months

Isoniazid & 3 months Once weekly  12 doses

rifapentine*

• *Rifapentine is not currently registered in Malaysia.

• *Its use should be restricted to those on DOT 120
 TAKE HOME MESSAGES
1. Sporadic reactivation is a cause of continuous
dissemination of TB in Malaysia.

2. Treatment of LTBI may be incorporated into TB

elimination programme.

3. Nonetheless, longitudinal study is needed to

prove the long-term effectiveness of this
strategy.
121
 FOLLOW-UP,
REFERRAL &
COMMON ADR OF
ANTITB TREATMENT

122
 FOLLOW-UP
• All patients on antiTB treatment should be
monitored to assess their response to
treatment & to identify problems associated
with it.

• All patients should be aware of symptoms

indicative of PTB & adverse drug reactions.

123
 MALAYSIAN CPG TB 2002
• Follow-up was recommended at 2, 4 & 6
months during treatment. Sputum smear &
chest radiograph were recommended to be
done during each follow-up clinic visit.

124
 MALAYSIAN CPG TB 2012

• In order to detect early adverse drug reactions

& to enhance compliance, follow-up within
1 month of starting treatment is advisable.

• Sputum smear & chest radiograph should be

done at 2 & 6 months if patient is clinically
improving.
•

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FLOW CHART FOR 6 MONTHS
TREATMENT OF PTB

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 FOLLOW-UP
• Patients with initial sputum smear negative
should have repeat sputum smear at 2
months of antiTB treatment. If still negative,
no further sputum sample is required.

• If sputum smear remains positive at 2 months,

refer to specialists with experience in TB
management & repeat sputum AFB & sputum
MTB C&S at 3 months.

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 FOLLOW-UP
• Patients with initial sputum positive should
have repeat sputum smear at 2 & 6 months of
antiTB treatment.

• Patients who remain sputum smear positive

should be referred to specialists with
experience in TB management.

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 FOLLOW-UP AFTER COMPLETION
OF ANTITB TREATMENT
• Follow-up clinic visits should not be conducted
routinely after treatment completion.

• Patients should be told to watch for

symptoms of relapse & how to contact the TB
service rapidly through primary care or a TB
clinic.

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 DEFINITION OF
ADVERSE DRUG REACTION (ADR)
• A response to a medicine which is unintended
or harm which occurs at a normal dosage
during normal use.

ONSET OF ADR FOR ANTITB

• ADRs occur within early stage of the
treatment compared to the later stage.
Kishore PV et al., Pa J Pharm Sci, 2008

130
CLASSIFICATION OF ADR FOR ANTITB

Treat
symptomatically
WITHOUT
treatment
interruption

131
 RISK FACTORS OF ADR FOR ANTITB
• Age >40 years
• Overweight/obesity
• Smoking
• Alcoholism
• Anaemia
• Baseline ALT more than
twice upper limit of normal
• Baseline aspartate
aminotransferase more
than twice upper limit of
normal
• EPTB
• MDR-TB medication
• HIV infection
• CD4 count <350 cells/mm3
• Hepatitis B virus infection
• Hepatitis C virus infection
• Concomitant use of other
hepatotoxic drugs
Chung-Delgado K et al., PLoS ONE, 2011
1
2
Vilarica AS et al., Rev Port Pneumol, 2010
3
Khalili H et al., Factors DARU, 2009
4
Marzuki OA et al., Singapore Med J, 2008
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 SYSTEMS MOST AFFECTED BY
ANTITB DRUGS
• Hepatobiliary
• Skin
• Gastrointestinal tract
• Skeletal system
• Renal

Shang P et al., PLoS ONE, 2011

1

2Teleman MD et al., Int J Tuberc Lung Dis, 2002

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 DRUG-INDUCED RASHES
Pyrazinamide (MOST)
Drug-Induced

Algorithm
Severe Cutaneous ADRs

Discontinue antiTB until the rashes subside

Reintroduce individual drug sequentially to identify the offending drug

Provide suitable regimen when an offending drug is identified

(If possible, regimen should include 2 most potent drugs namely
isoniazid & rifampicin )
Yee D et al., Am J Respir Crit Care Med, 2003
134
 DRUG-INDUCED RASHES (cont.)

Desensitisation?
 If the offending drugs are both isoniazid &
rifampicin
 If a suitable drug combination is available, it is not
necessary to perform desensitisation
 It is done by careful administration of increasing
doses of the drug under close supervision
 Complex Cutaneous ADRs requires specialists
consultation

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 DRUG-INDUCED HEPATITIS

Risk Factors1,2 Drug-Induced

• Slow acetylators Pyrazinamide (MOST)
• Old age
• Extensive TB disease Isoniazid
• Malnutrition
• Rifampicin (LEAST)
Alcoholism
• Chronic viral hepatitis B & C
infections Monitoring
• Pregnancy until 90 days At least for the first 2 - 4 weeks is
postpartum recommended among all patients with
• HIV antiTB treatment as DIH usually occurs
• Organ transplant recipients within the initial 2 months of treatment.

1
Yew WW et al., Respirology, 2006
2
Blumberg HM et al., Am J Respir Crit Care Med, 2003
136
 DRUG-INDUCED HEPATITIS (cont.)

Restarting?
• Depends on whether hepatotoxicity sets in
during the initial or the continuation phase
of treatment & the amount of treatment
received prior to the onset of such toxicity.

137
 DRUG-INDUCED HEPATITIS (cont.)

When to Stop AntiTB?

• Serum transaminase level reaches 3
x ULN for patients with symptoms
suggestive of hepatitis
• Serum transaminase level reaches 5
x ULN for those without symptoms

Restarting
The patient can then be retreated with a
regimen containing fewer potentially
hepatotoxic drugs such as streptomycin,
ethambutol, isoniazid & fluoroquinolones.
138
DRUG-INDUCED HEPATITIS (cont.)

139
 WHEN TO REFER
The following conditions should be referred to
specialists with experience in TB management:
•Unsure of TB diagnosis
•Retreatment of TB
•Adverse events following antiTB drugs
•MDR- & XDR-TB
•EPTB except TB lymphadenitis

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 WHEN TO REFER
• Renal &/or liver impairment with TB
• HIV-TB co-infection
• Smear negative TB
• Smear positive TB after 2 months of antiTB
treatment
• All children diagnosed as TB
• Maternal TB
• Complex TB cases requiring surgical
intervention
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 TAKE HOME MESSAGES
• All patients on antiTB treatment should be monitored to assess their
response to treatment & to identify problems associated with it.

• All patients should be aware of symptoms indicative of PTB &

adverse drug reactions.

• WHO recommends daily dosing throughout the course of antiTB

treatment.

• Follow-up clinic visits should not be conducted routinely after

treatment completion.

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 THANK YOU

tengkusaifudin@yahoo.co.uk
rahelaambaraskhan@yahoo.com

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