Rina Triasih, MMed(Paed), PhD, SpAK

Department of Pediatric
Sardjito Hospital Faculty of Medicine
Universitas Gadjah Mada Yogyakarta

Education
Medical Doctor Universitas Gadjah Mada, 1993
Pediatrician Universitas Gadjah Mada, 2003
Master of Medicine in Pediatric - The University of Melbourne, 2008
PhD The University of Melbourne, 2013

Training and Fellowship

Intensive course on Immuno-diagnostic - 2005
Pediatric Respirology Royal Children Hospital Melbourne, 2006 2008
Childhood Tuberculosis Capetown, South Africa, 2009
Clinical Research &EBM Inst. of Trop Medicine, Antwerp, Belgium, 2009
Updates on Child Tuberculosis
in Indonesia

Rina Triasih
 Outline

Why should we update the guideline ?

The Updates:

Diagnosis approach

Isoniazid Preventive Therapy

Multidrug-Resistant TB in children
Why should we update
the guideline ?
 Tuberculosis :
An old disease - new twists

One third of the worlds population is infected

TB kills 5,000 people a day 2-3 million/year
Hundreds of thousands of children will become
TB orphans
The challenges in TB global control:
HIV and TB co-infection
Multi-drug resistance TB (MDR TB)
 Global Drug-Resistant TB:
How Bad Is It?
700000
630000

600000

500000 424203

400000
272906
300000

200000

100000

0
1 2 3
2000 2004 2010
(1.1%) 4.3%)
(5.3%)
WHO. 2013. Update on MDR-TB. ; CDC. MMWR Morb Mortal Wkly Rep. 2013;62:1-12.
Wells CD. Curr Infect Dis Rep. 2010;12:192-197.
Estimated number of child TB
globally

Lancet 2014; 383: 157279

CHILD TUBERCULOSIS:
INDONESIA SITUATION
 Proportion of childhood TB cases among all TB cases, 2015*
Indonesia 9,0
Papua 17,3
Papua Barat 17,3
Jawa Barat 15,2
Bangka Belitung 11,7
DKI Jakarta 11,2
Banten 9,1
DIY 9,1
Bengkulu 9,1
Kalimantan 8,9
Jawa Tengah 8,6
Sumaterra Barat 8,2
Kalimantan Timur 8,1
Kalimantan 7,1
Lampung 6,7
Maluku 6,7
NTT 6,6
Maluku Utara 6,4
Sumatera Selatan 6,3
Kep Riau 5,8
Jawa timur 5,7
Bali 5,3
Sulawesi Tengah 5,2
Kalimantan Barat 5,0
Jambi 4,7
Riau 4,6
Sulawesi Selatan 4,6
Kalimantan Utara 4,4
Sumatera Utara 3,8
NTB 3,6
Sulawesi Barat 2,1 *data per 30 May 2016
Gorontalo 1,9
Sulawesi Utara 1,7
Sulawesi 1,4
Aceh 1,2
 Proportion
All Cases TB Childhood Child TB case per
No Province #districts Childhood
(2014) TB(2014) district per year
TB
1NAD 23 5,194 69 1.3% 3
2SUMUT 33 21,910 460 2.1% 14
3SUMBAR 19 6,891 485 7.0% 26
4RIAU 12 5,136 126 2.5% 11
5KEPRI 7 2,773 110 4.0% 16
6JAMBI 11 3,051 85 2.8% 8
7SUMSEL 17 8,566 465 5.4% 27
8BABEL 7 1,511 168 11.1% 24
9BENGKULU 10 1,987 91 4.6% 9
10LAMPUNG 15 6,499 217 3.3% 14
11BANTEN 8 9,597 609 6.3% 76
12DKI JKT 6 19,605 1,494 7.6% 249
13JABAR 27 62,904 8,650 13.8% 320
14JATENG 35 29,994 1,396 4.7% 40
15DIY 5 2,562 167 6.5% 33
16JATIM 38 41,614 2,071 5.0% 55
Recording and reporting
New diagnostic tools
 Diagnosis of TB in children
Confirmed:
Sputum smear (+)/Xpert MTB/RIF (+)/Culture (+)

Clinically:
1. TB symptoms
2. Evidence of infection: TST (+) OR close
contact (+) OR IGRA (+)
3. CXR: suggestive of TB
 Rapid molecular test
- Xpert TB/RIF
identifies M tuberculosis and rifampin
resistance using cartridge-based real-time
PCR
Result within 2-3 hours

Line-probe assays (eg, Hain GenoType)

identify genotypic resistance to both
isoniazid and rifampin
 Xpert MTB/RIF machine in Indonesia
Kalimantan Barat:
RS Soedarso
Pontianak
Kalimantan Timur
RS Syahrani,
Sumatera Barat: Samarinda
RS Achmad Jawa Tengah:
Mochtar RSJambi:
Moewardi
Aceh: RS Mataher
RS Kariadi
RS Zainoel Riau: RS Cilacap Sulawesi Utara
Abidin RS Arifin RSUD Kudus RS Kandou
Achmad RS Ario Wirawan Salatiga Papua Barat
Sulawesi
Tengah RS Kabupaten
RS Undata Sorong
Papua
Bangka
BLK Jayapura
Belitung:
RS Depati
Hamzah Sumsel
RS M
Husein
Sumatera
Utara:
RS Adam Malik Sulawesi Barat:
RS Sulawesi Sulawesi
Lampung: Bengkulu: Barat Tenggara:
RS Abdul RS M Riau Islands: RS Bahtera
Moeloek Yunus Mas
RS Embung
Fatimah NTT
Yogyakarta: Maluku:
RS Johannes,
DKI Jakarta: Mikrobiologi UGM NTB: RS Haulussi
Kupang
RS Persahabatan RS NTB
Mikrobiologi UI Bali:

82 machines in
Jawa Timur: RS Sanglah
RS Pengayoman
RS Soetomo South
Jawa Barat: BBLK Surabaya Sulawesi:

33 provinces
RS Hasan Sadikin RS Saiful Anwar RS Labuang
BLK Bandung RS Jember Baji
RS Gunawan Bogor RSUD Soedono Madiun NHCR
Diagnosis: problems & challenges

In children often difficult because of:

Challenges in obtaining respiratory
specimens
The paucibacillary nature of childhood TB
Low yield of positive culture: 30 50%
Lack of resources for sputum collection and
microbiological tests
 The Indonesia Scoring System

0 1 2 3
Contact No or - AFB (-) OR AFB(+)
not clear reported
TST negative - - positive
Weight - W/A < 80% W/A < 60% -
Fever - > 2 weeks - -
Cough < 3 wks >3 wks - -
Lymphnode - multiple, >1cm, - -
enlargment tenderness (-)
Joint - edema - -
CXR normal sugestive - -
 The Scoring system: Problems
PPD solution and CXR machines are not
available in all Puskesmas

Lack of confidence among general physician to

diagnose without TST and CXR

Over-diagnosis and underdiagnosis

Update on the diagnosis
approach
 One or more of these symptoms:
Cough > 2 weeks
NEW APPROACH Fever 2 weeks
OF CHILD TB
No weight gain or weight loss in the previous 2 months
DIAGNOSIS IN
INDONESIA (1)
Malaise 2 weeks
The symptoms persist despite adequate treatmetn

Rapid molecular test

(Xpert mTB/RIF)

Specimen cant be
Positive Negative collected

Bacteriology Access for TST and No access for TST and

CXR available*) CXR
confirmed TB

Anti TB treatment
NEW APPROACH
OF CHILD TB
DIAGNOSIS IN Access for TST and No access for TST and
INDONESIA (2) CXR available*) CXR

Contact to an No/Unclear contact

adult pulmonary to an adult
TB patient pulmonary TB
patient

Observe symptoms
for 2 weeks

Persist Improved

Clinical TB
Not TB

Anti TB treatment
NEW APPROACH
OF CHILD TB
DIAGNOSIS IN Access for TST and CXR No access for TST and
INDONESIA (3) available*) CXR

Scoring System

Score 6 Score <6

TST TST (-)

OR AND
Contact (+) Contact (-)

Observe symptoms for

2 wks

Clinical TB
Persists Improved
Anti TB
treatment
Not TB
Isoniazid Preventive Therapy
(IPT)
 How to manage a child contact ?

Contact investigation !

1. Investigate for infection/disease

2. Provide appropriate treatment: ATT or IPT

 WHO symptom based screening

Children in close contact with a case of sputum smear-positive TB

Less than 5 years More than 5 years

Well Symptomatic Symptomatic Well

Preventive therapy Evaluate for TB disease No treatment

If becomes symptomatic If becomes symptomatic

 Management of child contact

Age HIV Outcome of Management

investigation
Balita (+)/(-) LTBI IPT
Balita (+)/(-) Exposed only IPT
> 5 th (+) LTBI IPT
> 5 th (+) Exposed only IPT
> 5 th (-) LTBI observe
> 5 th (-) Exposed only observe
IPT: INH 10 mg/kg BW/day for 6 months
Mutli-drug Resistance TB
 Definitions
Mono-resistant TB
Resistant to one of the anti TB medications
Poly-resistant TB
Resistant to > 2 anti TB medications
Multidrug-resistant TB (MDR TB)
resistant to isoniazid and rifampicin
Extensively drugresistant TB (XDR TB)
MDR-TB plus resistance to fluoroquinolones and an
injectable agent (amikacin, kanamycin, or
capreomycin)
 MDR TB in Indonesia
The 8th of the 27 countries with hghest MDR-TB
cases
Number of cases in children:
Yogyakarta: 2
DKI: 6
East Java: 2
West Java: 4
Medan : 1
Papua: 1
West Sumatra: 1
 Criteria for suspected MDR-TB
in children
Previous TB treatment in the past 6-12 months
Close contact with a person known to have MDR-TB
Close contact with a person who has died from TB,
failed TB treatment, or is non- adherent to TB
treatment
Failure to improve (including persistence of positive
smears or cultures, persistence of symptoms, and
failure to gain weigh) after 2-3 months of first-line TB
treatment, despite of good adherence.
 Anti TB drugs (WHO 2016)
Group Drugs

A. Fluoroquinolone levofloxacin, moxifloxacin, gatifloxacin

B. Second-line injectable agents amikacin, capreomycin, kanamycin,
(streptomycin)
C. Other core second-line ethionamide (or prothionamide),
agents cycloserine (or terizidone), linezolid,
clofazimine
D. Add on agents (not part D1 Pirazinamid
of the core regiment) Ethambutol
D2 bedaquiline, delamanid

D3 p-aminosalicylic acid, imipenem

cilastatin, meropenem, amoxicillin
clavulanate, (thioacetazone).
 General principles of treatment

Composed of at least five drugs:

Four core second-line drugs
Plus pyrazinamide.
All treatment is daily and under direct observation
Counsel and support patients/parents at every visit
regarding adverse effects and importance of adherence
Management at a specialized MDR-TB clinic
 Designing a Treatment Regimen
for MDR-TB

One of GroupA One of Group B Two of group C

Levofloxacin Amikacin Ethionamide
Moxifloxacin Kanamycin Prothionamide
Capreomycin Cycloserine/terizidone
Streptomycin Para-aminosalicylic acid

Group D1
Ethambutol
Pyrazinamide

Group D2 and D2 if cannot

be commposed from
above
bedaquiline, delamanid
p-aminosalicylic acid, imipenem
cilastatin, meropenem, amoxicillin
clavulanate, (thioacetazone).
 Duration of treatment
Optimal duration of treatment in children is
not known
Conventional: 18-24 months
Shorter regimen: 12 months

Intensive phase including 2nd line injectable

drug, continuation phase mainly stop
injectable drug
 Conclusion

Find and diagnose the case properly

Treat and monitor properly,

including latent TB infection

Notify to NTP
 Are we doing enough ?

Many things we need can wait.

The Child cannot.
Right now is the time his
bones are being formed,
his blood is being made,
and his senses are being developed.
To him we cannot answer
Tomorrow.
His name is Today.

- Gabriela Mistral -
Thank You