DIAGNOSTIC TOOLS FOR TB:

- TB INFECTION
- CONFIRMED TB
Workshop on Child TB
IPRM 2017
TST and IGRA are indirect measures of
TB infection: Immunodiagnostics
 DASAR IMUNOLOGI IGRA

o Individu dg infeksi TB memiliki limfosit yg akan bereaksi

terhadap stimulasi antigen
o QFT memiliki teknologi yg dapat menstimulasi sampel darah
dengan antigen spesifik TB: ESAT-6, CFP-10, TB7.7
o T-cell yang telah terstimulasi antigen spesifik tersebut akan
mengeluarkan IFN-
o Kadar dari IFN- yang terbentuk akan diukur untuk menilai
adanya infeksi M. tuberculosis
Procedure
 QFT Blood Collection Tubes
QFT 3-tube system
TB Antigen tube
Contiains antigen peptide: ESAT-6, CFP-10, TB7.7
To asses IFN- response to TB specific Ag

Mitogen control tube

As an indicator of mistakes in sample
management and incubation

Nil control tube

As back ground noise
INTERPRETASI HASIL PEMERIKSAAN

Positif Ada infeksi M. TB

Negatif Tidak ada Infeksi M. TB

Sampel tidak responsif

Indeterminate
terhadap paparan Antigen
 Diagnostic values
Sensitivity meta-analysis IGRA TST

Diel et al, 2010, Chest-Developed country 84.5% 71.5%

Sester et al, 2011, ERJ 80% 68%

Spesifisitas meta-analysis IGRA TST

Diel et al, 2010, Chest-Developed 99.2% ND

country
Pai et all, 2008, Ann Intern Med (BCG ND 59%
vaccinated)
US CDC Guidelines 99% 86%
Diel et al, 2011, ERJ 99.4% 88.7%
 LIMITATIONS of IGRAs are the same as the TST ..

CANNOT distinguish between active and latent

TB
CANNOT rule-out active TB and latent TB in
immunocompromised persons
CANNOT distinguish between recent and old
infection
SHOULD NOT be used to determine efficacy of
treatment
However, IGRAs CAN distinguish between BCG, NTM
and true TB infection
Xpert MTB RIF
Kebijakan Penggunaan Xpert MTB/RIF di
Indonesia
Sebagai alat diagnosis cepat untuk terduga:
TB Resistan Obat
TB pada ODHA
TB pada anak
TB dengan hasil BTA negatif setelah pemeriksaan
mikroskopis
TB ekstraparu
TB dengan komorbiditas
TB di rutan/lapas
TB kasus baru
 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.
Xpert MTB/Rif: workflow

Boehme CC et al 2010. N Engl J Med 363(11):1005-15

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

Sumatera Utara:
RS Adam Malik Sumsel
RSSulawesi
M Barat:
Husein
RS Sulawesi Barat Sulawesi
Lampung: Tenggara:
RS Abdul RS Bahtera Mas
Riau Islands:
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, Keterangan:
RS Soetomo
2012-2016 sudah
Kupang
South Sulawesi:
Jawa Barat: BBLK Surabaya RS Labuang
RS Hasan Sadikin
BLK Bandung
RS Saiful Anwar
RS Jember
Baji operasional 82 mesin
NHCR
RS Gunawan Bogor RSUD Soedono Madiun di 33 provinsi. Belum
tersedia di Kaltara
 Interpretasi hasil pemeriksaan TCM dengan Xpert MTB/RIF
WHO recommended
regimen for MDR-TB with
INH;
Modify treatment based on
Registration as RR-TB
In groups with high the DST results;
risk of MDR-TB Update registration
DST to at least INH;
Quinolones; SL injectable WHO recommended
regimen for MDR-TB
with INH;
Registration as RR-TB
TB Modify treatment
TB detected; based on the DST
detected; Rif results;
Rif resistant Update registration
resistant
Repeat
In groups with low DST to at least RIF; INH;
risk of MDR-TB
Xpert In case of discordance
Quinolones; SL injectable
Xpert MTB/RIF on Rif result refer sample
for sequencing
MTB/RIF TB
detected;
assay TB
Rif
sensitive
detected;
Rif
sensitive
WHO recommended
first-line treatment;
TB not Registration as
detected bacteriologically
confirmed TB

Further investigation (CXR,

If TB still
repeat Xpert MTB/RIF,
suspected
culture, etc..)
MDR TB
 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
Sputum induction
Video sputum induction