DR SHAM SU LIA

MANAGEMENT APPROACH OF Pakar Perubatan Keluarga UD54

Klinik Kesihatan Bandar Tun Abdul
TUBERCULOSIS IN PRIMARY CARE Razak
Rompin, Pahang
OUTLINES:
• Diagnosis of pulmonary TB
• TB case management in primary care
• TB in special situations
• Isoniazid prophylaxis therapy (IPT)
DIAGNOSING PULMONARY TB
• Symptoms of TB
HISTORY
• Risk of exposure
• High risk group

• BCG scar
PHYSICAL • Palpable LN
EXAMINATION • Lung auscultation
• Hepatosplenomegaly

• Sputum for direct smear

• Sputum for MTB culture
INVESTIGATION
• CXR
• Others as indicated
 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)
1
WHO, 2010

4
 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

5
 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

6
7
Normal Chest X-ray

NORMAL CXR
GRADING OF PTB SEVERITY FROM CXR

qMinimal
÷Slight lesions with NO cavity.
÷Confined to small parts of one or both lungs.
÷Total extent of lesion not exceeding the upper zone.
qModerate
÷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.
qAdvanced
÷Lesions are more extensive than moderately advanced.
Figure 1. High-resolution CT scan (far left) and drawings of the lung (middle left), a budding tree
(middle right), and tree buds (far right) show the tree-in-bud pattern.
 TREE-IN-BUD APPEARANCE
Figure 2. Postprimary active tuberculosis in a 66-year-old woman with a chronic cough.

Rossi S E et al. Radiographics 2005;25:789-801

 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 failure A patient who has received Category I treatment for TB
& in whom treatment has failed.

Treatment after default A patient who returns to treatment, bacteriologically

positive by sputum smear microscopy or culture,
following interruption of treatment for 2 or more
consecutive months.
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 HEALTH EDUCATION
• Must be given to the patient and family members/carers at the time
of starting treatment.
• This should include:-
a. nature of the disease
b. necessity of strict adherence with the prolonged treatment
c. risks of defaulting treatment
d. side effects of medication
e. risks of transmission and need for respiratory hygiene as well as
cough/sneeze etiquette
OPTIMAL DURATION

21
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

22
 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
• Duration of treatment for bone & joint TB is 9 months
• Peripheral LN and soft tissues TB – 6 months
• Miliary & disseminated TB – 9-12 months

1
World Health Organization. Treatment of tuberculosis Guidelines. Fourth ed. 2010
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

23
DIRECTLY OBSERVED THERAPY (DOT)

24
 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

25
FDC IN MOH

4-Drug combination: 3-Drug combination:

isoniazid 75 mg, isoniazid 75 mg,
rifampicin 150 mg, rifampicin 150 mg &
pyrazinamide 400 mg & pyrazinamide 400 mg
ethambutol 275 mg tablet tablet

26
 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

• Intensive phase: 56 doses

• Maintenance phase: 126 doses

27
Management of Tuberculosis (Third Edition)

Visit Duration Regimen Investigations

1. 0M EHRZ/SHRZ FBC, RBS, RP, LFT, HIV

Sputum AFB direct smear
Sputum MTB C&S
CXR

2. 2 - 4 weeks EHRZ/SHRZ LFT

3. 2M HR H3R3 LFT if necessary, CXR

Sputum MTB C&S if smear

remains positive

4. 4M HR H3R3 Sputum AFB direct smear and

CXR only if there is no clinical
improvement

5. 6M Completion of 6 months Sputum AFB direct smear

treatment CXR

Patients with initial sputum smear negative should have repeat sputum smear at two months
of antiTB treatment. If still negative, no further sputum sample is required.
MANAGEMENT OF TB IN SPECIAL
SITUATIONS
 TREATMENT AFTER INTERRUPTION

• Interruption in intensive phase:

– If ≥14 days, to restart from beginning i.e. Day 1.

– If <14 days, to continue form last dose.

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 TREATMENT AFTER INTERRUPTION
• 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.

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 MANAGEMENT TB INFECTIONS IN DIABETIC
• Delay sputum conversion among poorly controlled diabetics
• Advance CXR changes @ large cavity
• Sputum conversion rate at 2 months intensive – 71.8-91.3%

• Mx – change to maintenance,
• send MTB C+S,
• trace baseline MTB C+S
 MANAGEMENT OF TB WITH HIV CO-INFECTION

CD4 count Timing of HAART initiation

(cells/µl)
<50 2 weeks after starting intensive phase of antiTB
treatment
>50 but <350 After completion of intensive phase of antiTB
treatment
>350 Continue antiTB treatment & monitor CD4.
Commence HAART if CD4 drops <350 cells/µl.
 LIVER IMPAIRMENT
• Unstable or advanced liver disease - baseline LFT prior to
treatment1

• Regular monitoring at weekly & biweekly intervals during the

initial 2 months2

• Then more widely spaced assessments throughout the rest of

treatment period
1
WHO, 2010
2
Yew WW et al., Respirology, 2006

34
 LIVER IMPAIRMENT
• If baseline LFTs are more than 3X upper limit of normal before
initiation of therapy, a regimen containing fewer hepatotoxic
drugs can be considered

• The likelihood of drug induced hepatitis is greater & is potentially

life threatening

• Expert consultation is usually needed

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 ANTITB DRUGS IN LIVER IMPAIRMENT
Drugs Duration
Isoniazid & rifampicin, plus 9 months Ethambutol given
ethambutol until isoniazid
susceptibility is
documented
Isoniazid, rifampicin, 2 months
streptomycin &
ethambutol,
Progressively followed by isoniazid & 6 months
more severe rifampicin
liver disease Rifampicin, pyrazinamide & 6-9
ethambuthol months
Isoniazid, ethambutol & 2 months
streptomycin,
followed by
isoniazid & ethambutol 10 months
Streptomycin, ethambutol 18 - 24
& fluoroquinolones months 36
 RENAL IMPAIRMENT

• Regimen for patients with renal failure includes 2 months of

isoniazid, rifampicin, pyrazinamide & ethambutol followed by 4
months of isoniazid & rifampicin1

• Significant renal excretion of ethambutol & metabolites of

pyrazinamide occurs, hence doses must be adjusted to
intermittent dosing

1WHO, 2010

37
 RENAL IMPAIRMENT

• Pyrazinamide should be administered after hemodialysis to avoid

premature drug removal1

• All 4 antiTB drugs can be administered after hemodialysis to

facilitate DOT

• Avoid streptomycin
1
Malone RS et al., Am J Respir Crit Care Med, 1999

38
 ANTITB DRUGS IN RENAL IMPAIRMENT
Recommended dose &
Drug Change in frequency?
frequency 1

Isoniazid No change Max 300 mg PO once daily

Rifampicin No change Max 600 mg PO once daily

25 - 30 mg/kg per dose PO 3

Pyrazinamide Yes
times per week

15 - 25 mg/kg per dose PO 3

Ethambutol Yes
times per week
1CrCl:Creatinine clearance by Cockcroft-Gault equation, intermittent dialysis
PO: by mouth
IBW: ideal body weight
Standard doses are given unless there is intolerance 39
SCREENING FOR TB CONTACT
 ISTILAH DEFINISI

KONTAK Individu yang terdedah kepada kes indeks sewaktu kes dalam
tempoh keberjangkitan

KONTAK Individu yang berkongsi kediamanan sekurang-kurangnya

SERUMAH semalaman atau lebih dengan kes dengan kes indeks sewaktu
(HOUSEHOLD kes indeks dalam tempoh keberjangkitan sehingga tamatnya
ISTILAH CONTACT) tempoh keberjangkitan
TEKNIKAL
UNTUK
CLOSE CONTACT Individu yang tidak berkongsi kediaman dengan kes indeks
PENYAKIT tetapi berkongsi ruang yang sama iaitu sekurang-kurangnya 15
BERJANGKIT jam seminggu atau keseluruhan 180 jam sewaktu kes indeks
dalam tempoh keberjangkitan. Merangkumi kontak pekerjaan,
kontak social dan lain-lain. (Fiske 2014)

KONTAK KASUAL Individu yang terdedah kepada kes indeks melalui aktiviti social
samada rakan, menaiki kenderaan yang sama, berada dalam
ruang yang sama, rakan sekursus dan lain-lain yang tidak
memenuhi kriteria bagi close contact.
HIGH RISK GROUP FOR TB INFECTIONS

Recommendation 19
(new)
(Strong recommendation, very
low quality of evidence)
Recommendation 20
(new)
(Conditional recommendation,
very low quality of evidence)
SCREENING FOR TB CONTACT:
4
It is recommended that contact investigation be conducted for
household and close contacts when the index case has any of the
following characteristics:
- has sputum smear-positive pulmonary TB;
- has multidrug-resistant or extensively drug-resistant TB (proven or
suspected);
- is a person living with HIV; or
- is a child <5 years of age
Contact investigation may be conducted for household and close
contacts of all other index cases with pulmonary TB, in addition to
the index cases covered in Recommendation 19
 2.3.1 Cadangan yang diberi oleh WHO

JADUAL 4

Recommendation 21 Children <5 years of age who are household or close contacts of
(new) people with TB and who, after an appropriate clinical evaluation,
(Strong recommendation, are found not to have active TB should be given 6 months of IPT (10

ISONIAZIDE high quality of evidence) mg/kg per day, range 7 15 mg/kg, maximum dose 300 mg/day)

PROPHYLAXIS: Recommendation 25
(new)
(Strong recommendation, Children living with HIV who are more than 12 months of age and
low quality of evidence) who are unlikely to have TB disease on symptom-based screening
and who have no contact with a TB case:
*IPT is for treating LTBI
- should be offered 6 months of IPT (10 mg/kg per day, range 7 15
and children living with mg/kg, maximum dose 300 mg/day) as part of a comprehensive
HIV package of HIV prevention and care services if living in settings with
a high TB prevalence
* Children on IPT (Conditional -might be offered 6 months of IPT (10 mg/kg per day, range 7 15
should be follow-up recommendation, mg/kg, maximum dose 300 mg/day) as part of a comprehensive
every 2 months low quality of evidence) package of HIV prevention and care services if living in settings with
a medium or low TB prevalence

2.3.2 Rujukan kes untuk pemberian IPT

7.1 CARTA ALIR PENGURUSAN KONTAK DI KALANGAN KANAK-KANAK

Kontak Tibi di kalangan

kanak-kanak

0-4 tahun 5-14 tahun

Saringan (satu atau lebih)

Simtomatik
AFB
CXR
Rujuk ke Mantoux
Pakar utk *Gene-Xpert
IPT *IgRA (hanya utk 5 ke
atas)

TIDAK Rujuk ke Pakar

Positif TB? YA utk mulakan
ubat Tibi

Aturkan saringan
susulan mengikut
kekerapan
0, 3, 6, 12
 Algorithm 5: Investigations For Contact Tracing in Adults

PTB Close Contact*

Symptomatic Asymptomatic

Evaluate for active TB Mantoux test

CXR
61

Sputum AFB
Mantoux test
(optional) ≥10 mm <10 mm

Management of Tuberculosis (Third Ed

Chest x-ray Discharge
with advice**
Diagnosis Diagnosis
confirmed – treat inconclusive –
refer specialist
Normal – Abnormal –
manage as latent evaluate for
TB infection active TB
 Algorithm 6: Management of Children with Positive History of Contact with Tuberculosis

Child (Contact)

Mantoux Test

≥10 mm <10 mm

CXR

Normal Abnormal Symptomatic Asymptomatic

l

CXR Check BCG

Asymptomatic Symptoms
suggestive of TB

Normal Abnormal No scar Scar present

≥5 years old <5 years old

Follow-up Treat as LTBI Treat as TB Investigate Refer to BCG Follow-up

further Paediatrician
 BCG at the end of treatment.

<2
months

Smear Smear
negative just positive - - -

delivery
No prophylaxis Give prophylaxis: Give prophylaxis: Isoniazid for six months
for infant Isoniazid for six months
OR isoniazid for three
months followed by TST
BCG at birth Defer BCG at birth, give Reimmunise If BCG given at birth,
after stopping isoniazid with BCG after no need to reimmunise
stopping isoniazid
THANK YOU…