UPI – 7 December 2019

“Update in management of
pulmonary and extra-pulmonary
TB in children”
Madeleine Ramdhani Jasin, MD (Paediatrician)
Respirology Division, Paediatric Department
Cipto Mangunkusumo Hospital – Universitas Indonesia
CURRICULUM VITAE
Dr Madeleine Ramdhani Jasin, SpA
◎E-mail : madeleinejasin@gmail.com
EDUCATION AND COURSES
◎2002-2008 : Medical School, Universitas Indonesia
◎2010-2014 : Pediatric Residency, Medical School, Universitas Indonesia
◎May – July 2016 : Workshop in Basic Bronchoscopy, RSCM, Jakarta
◎October 2016 : 3 Pediatric Flexible Bronchoscopy Course; NUH, Singapore
rd

◎April – October 2018 : Fellowship, Paediatric Pulmonary and Sleep; NUH, Singapore
WORKING EXPERIENCE
◎2015 – current : Respirology Division, Pediatric Department, RSCM
ORGANISATION
◎2018 – current : Secretary of Respirology task force, IRS branch Jakarta
 “
“A world free of Tuberculosis. Zero deaths,
diseased, and suffering due to Tuberculosis”

3
Magnitude of Tuberculosis (1)

7.5 billions world population

www.who.int
4
Magnitude of Tuberculosis (2)

www.who.int
5
Tuberculosis burden in Indonesia

https://www.tbindonesia.or.id/page/view/11/situasi-tbc-di-indonesia 6
htt[p://www.who.int
The importance of
managing TB in
children
11% of population

1. TB frequently progresses from latent infection to

disease
2. Severe manifestations in children – Sentinel cases
3. Indicating recent and/or ongoing transmissions in the
community www.who.int
Adams LV, Starke JR. Tuberculosis disease in children. https://www.uptodate.com/contents/tuberculosis-disease-in-children?source=history_widget 7
“What you/ we can
do as physician?”
A 2 yo boy with fever, https://dinkes.malangkota.go.id/2015/09/17/puskesmas-mulyorejo/

mum is treated with TB

AFB (+), otherwise he is
active
1. Quality diagnosis
2. Quality treatment
3. Active case finding
https://www.tribunnews.com/regional/2017/04/26/penderita-penyakit-tuberkulosis-meningkat-ppti-dan-
dinkes-kota-bogor-lakukan-gerakan-ketuk-pintu

8
 “Making
TB Diagnosis
In Children”

9
Pathogenesis
M. tuberculosis inhalation

phagocytosis by PAM bacilli dead

Tuberculosis live bacilli

incubation period
P
multiplies (2-12 weeks) r
primary focus formation i
lymphogenic spread m
hematogenic spread a
Primary complex r
TST (+) Cell Mediated Immunity (+) y

TB disease TB infection
T
B
primary complex complication
hematogenic spread complication Optimal immunity
lymphogenic complication

Dead
immunity 
reactivation/reinfection
Cured TB disease
Setyanto DB.
Tuberculosis. 2017
Natural history of Tuberculosis

• Symptom (-) • Symptom (-) • Symptom (+)

• TST/ IGRA (-) • TST/ IGRA (+) • TST/ IGRA (+)
• CXR (-) • CXR (-) • CXR (+)
• Bacteriology (-) • Bacteriology (-) • Bacteriology (+/-)
How to make Tuberculosis diagnosis (1)

• Cough > 2 weeks Perform

• Fever > 2 weeks bacteriological Positive results
• Decrease weight or examination
failure to thrive in
the last 2 months
Rapid molecular
• Malaise > 2 weeks
testing/ Xpert
Persisting with Acid fast bacili
adequate “TUBERCULOSIS
management M.Tb culture CONFIRMED
BACTERIOLOGICALLY”

12
How to make Tuberculosis diagnosis (2)

Negative results
• Cough > 2 weeks Perform
• Fever > 2 weeks bacteriological OR
• Decrease weight or examination No specimens
failure to thrive in taken
the last 2 months
Rapid molecular
• Malaise > 2 weeks
testing/ Xpert
Persisting with Acid fast bacili
adequate
management M.Tb culture “Access to chest X ray
OR tuberculin skin
test?”
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How to make Tuberculosis diagnosis (3)
THERE IS access to chest X ray OR tuberculin skin test

Score > 6 Scoring system Score < 6

Positive tuberculin Negative tuberculin

OR positive TB AND negative TB
contact contact

Observe for 2 weeks

TUBERCULOSIS
CLINICALLY Persisting No symptoms →
DIAGNOSED symptoms NOT TB 14
How to make Tuberculosis diagnosis (4)
NO access to chest X ray OR tuberculin skin test

Contact with
Yes adult TB patients No

Observe for 2
weeks

TUBERCULOSIS
Persisting No symptoms →
CLINICALLY
symptoms NOT TB
DIAGNOSED 15
Scoring system
0 1 2 3
Contact No or not - AFB (-) OR AFB(+)
clear parent’s report

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 - -
Total score
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17
What to Check in Extrapulmonary Tuberculosis
Extrapulmonary condition Samples

Lymphadenopathy, scrofuloderma Biopsy for histopathology examination, AFB, culture

Meningoencephalitis Cerebral fluid analysis, AFB, TB PCR, culture

Pleural effusion Pleural fluid analysis, adenosine deaminase

Pericardial fluid analysis, AFB, TB PCR, adenosine
Pericarditis deaminase
Biopsy for histopathology
Ascites fluid examination, AFB, TB PCR, adenosine
deaminase
Peritonitis
Stool TB PCR
Biopsy for histopathology
Renal Urine AFB, TB PCR, culture
Spondylitis Biopsy for histopathology

Cutis Biopsy for histopathology 18

 “Update in
Diagnosis of
Tuberculosis
in Children
19
Problem in Making Diagnosis
Difficult to get pulmonary sputum

Intrapulmonary Lack of sufficient tussive force to

produce adequate samples

Difficulty in Low bacteriological

obtaining samples confirmation

Usually require more invasive Usually

Extrapulmonary
method paucibacillary
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How to overcome difficulty in getting adequate
pulmonary samples?
◎ Sputum induction

Lahti et al, 2006, Turkey

• Sputum induction was able to perform in children age 6 mo – 15 yo for

pneumonia diagnosis

Jasin et al, 2015, Indonesia – RSCM

• Sputum induction is able to perform in 100% subjects, youngest 2 mo

• Alveolar macrophage > 5 cells is found in 97.5% subjects
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Sputum induction – How to do it (1)

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Sputum induction – How to do it (2)
1. Inhalation of
salbutamol and NaCl
0.9% for 15 mins
2. Inhalation of NaCl
3% for 15 mins
3. Mild massage to
chest
4. Suction sputum
through nose and
mouth OR
expectorate sputum
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Sputum induction – To look out
◎ Fasting for 3 hours prior to procedure
◎ Contraindicated to
○ Dyspnoea
○ SpO2 < 92%
○ Bleeding problems
○ Uncontrolled seizure
◎ Possible complications - RARE
○ Bronchospasm
○ Bleeding
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How to overcome low bacteriological confirmation?
Xpert MTB/Rif: workflow
o Automated nucleic
acid amplification
test
o Identify M.
tuberculosis & detect
rifampin resistance
o Better than smear
microscopy
o Rapid diagnosis
o Not to replace
culture
Boehme CC et al 2010. N Engl J Med 363(11):1005-15

25
 Sumatera Barat: GeneXpert in Indonesia
RS Achmad Jawa Tengah: Kalimantan Barat:
Mochtar RS Moewardi RS Soedarso
Aceh: RS Kariadi Pontianak
RS Cilacap Kalimantan Timur
RS Zainoel Riau: Sulawesi Utara
Abidin RSUD Kudus RS Syahrani,
RS Arifin RS Kandou
RS Ario Wirawan Salatiga Samarinda
Achmad
Sulawesi Papua Barat
Jambi: RS Kabupaten
Tengah
RS Sorong
RS Undata
Matahe Papua
Bangka r BLK Jayapura
Belitung:
RS Depati
Hamzah

Sumatera
Utara: Sumsel
RS Adam Malik RSSulawesi
M Barat:
Husein
RS Sulawesi Sulawesi
Barat Tenggara:
Lampung:
RS Abdul RS Bahtera
Riau Islands: Mas
Moeloek RS Embung
Fatimah Yogyakarta:
Bengkulu: Maluku:
DKI
RSJakarta:
M Mikrobiologi UGM NTB: RS Haulussi
RS Persahabatan
Yunus RS NTB
Mikrobiologi UI Bali: NTT
RS Pengayoman Jawa Timur: RS Sanglah RS Johannes,
RS Soetomo South Kupang
Jawa Barat: BBLK Surabaya Sulawesi:
RS Hasan Sadikin RS Saiful Anwar
BLK Bandung RS Jember
RS Labuang 2012-2016: 82 machine
Baji
RS Gunawan Bogor RSUD Soedono Madiun NHCR in 33 provinces
Update in confirming Tuberculosis infection

28
Tuberculin test vs. IGRA (1)
Kay, et al. Pediatrics. 2018

• In < 5 yo: sensitivity is similar in TST & IGRA (91% vs

91%)
• Sensitivity is reduced in < 2 yo
• In > 5 yo, IGRA is more sensitive (96% vs 83%)

WHO latent TB infection recommendation 2018

• Tuberculin or IGRA can be used to test latent TB infection

• Consider availability and affordability
Kay et al. Interferon gamma release assay performance for tuberculosis in childhood. Pediatrics. 2018;141.
WHO. Latent TB infection. 2018 29
Tuberculin test vs. IGRA (2)

Tuberculin IGRA

Unaffected by BCG
vaccination and
╳ √
Mycobacterium non-
Tuberculosis

Single patient visit ╳ √

Price + +++
Diagnosis of active TB
disease
╳ ╳
https://www.cdc.gov/tb/publications/factsheets/testing/igra.htm
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 “Update in
Treatment of
Tuberculosis
in Children”
31
Treatment for drug sensitive tuberculosis

RHZ

OR

RHZE RH
+
Steroid

Month -2 Month -6 Month -12 32

Anti-TB drugs: Dose and side effects
Daily dose Max dose
Drug (mg/kgBW/ (mg /day) Side effects
day)

Isoniazid 10 (7-15) 300 Hepatitis, peripheral neuritis, hypersensitivity

(H)
Rifampisin 15 (10-20) 600 Gastrointestinal reaction, hepatitis,
(R) thrombocytopenia, red orange secrete

Pirazinamid 35 (30-40) - Hepatic toxicity, arthalgia, gastrointestinal

(Z) reaction

Etambutol 20 (15–25) - Optic neuritis, decreased visus, color blind,

(E) hypersensitivity, gastrointestinal reaction
Duration of treatment
Intensive Maintenance
Diagnosis
phase phase
TB negative AFB
Lymphadenopathy TB
2HRZ 4HR
Pleuritis TB or TB with pleural
effusion
TB positive AFB
Destroyed lung TB
2HRZE 4HR
Extra-pulmonary TB other than
meningitis TB or skeletal TB
Skeletal TB
Milliary TB 2HRZE 10HR
Meningitis TB
Tuberculosis fixed
drug combination
Intensive phase
Maintenance phase
Weight (kg) (2 mo)
RH (75/50)
RHZ (75/50/150)
5-7 1 tablet 1 tablet
8-11 2 tablet 2 tablet
12-16 3 tablet 3 tablet
17-22 4 tablet 4 tablet
23-30 5 tablet 5 tablet
>30 Adult FDC* Adult FDC *

BW <5kg should be referred & need tailored dosing Don’t divide!

BW >30kg 6 ped FDC tablet, or use adult FDC tablet Don’t make pulveres/ powder!
Steroid is given in:
1. Meningitis TB
2.Endobronchial TB
3.Pericarditis TB
4.Milliary TB with respiratory distress
5.Pleural effusion
6.Abdominal TB with ascites

Follow up
◎ Follow up every 2 weeks for compliance, response, and side effects
◎ Documentation in TB DOTS form
How about MDR TB?

It is estimated that around 1,000,000 (95% CI:

938,000 – 1,055,000) children developed TB
disease, among whom 32,000 (95% CI: 26,000 –
39,000) children had MDR –TB
When we suspect MDR TB?

◎Previous TB treatment in the past 6-12

Confirm by rapid molecular testing

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 clinically after 2-3
months of first-line TB treatment,
including persistence of positive smears
or cultures, persistence of symptoms,
and failure to gain weight
 “Update in
Tuberculosis
prophylaxis”

39
How about prophylaxis for latent
tuberculosis infection?

10% of latent TB
infection will develop
disease
OPPORTUNITY TO
PREVENT DISEASE!

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 Take a look at this case

◎ A 3 months-old baby w/ resp distress

◎ Cough for 1 month, fever since 3 days pa
◎ The father was diagnosed TB with AFB +3 since 2
months
◎ Difficulty in weight gain
◎ The baby was never given TB prophylaxis drug
Working diagnosis
◎ Milliary TB
◎ Failure to thrive
Missed
opportunity
to be prevented
Kemkes RI 2016, Juknis manajemen TB anak
Indonesian Pediatrics Society recommendation of
latent tuberculosis infection

INH 10 mg/kgBW as chemoprophylaxis

◎ High –risk at 1-2 years after first infection,

newborn age, and first 5 years of life
◎ Other high-risk group are:
✓ TB-contact in same house
✓ Dormitory, orphanage, playing area, etc.
✓ Immunocompromised (e.g Immune
deficiency, HIV-infection, CKD,
malignancy, etc)
✓ Malnutrition
Algorithm for children contact to MDR case

Prophylaxis is given to:

◎ < 5 yo or immunocompromised
◎ Dose for Levofloksasin 15-20
mg/kgBW/day and Ethambutol 15-25
mg/kgBW/day for 6 months
◎ Prior to meal
◎ Observe Tuberculosis manifestations
and complications of medication
Remember to do active investigation in the
household/ community

http://4.bp.blogspot.com/_x468CNB13T8/S-NXQdR9FbI/AAAAAAAAAVA/Y5JRlX1HD-w/s400/Ibu%2Bmiskin.jpg
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SUMMARY
1. Tuberculosis is top infectious killer disease globally,
including in Indonesia. However, 32% cases are still not
notified
2. Paediatric TB shows on-going transmission
3. Sputum induction is safe to perform in children
4. Bacteriological confirmation should be done in pulmonary
and extrapulmonary TB
5. Strategy to eliminate TB is not only to treat active TB cases,
but also to manage latent TB infection
6. Contact investigation need to be done in all diagnosed TB
patients
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 “
Together to END TB

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