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Dr.dr. Prayudi Santoso, SpPD-KP, M.

Kes,FCCP, FINASIM
E-mail: prayudimartha@yahoo.com

Education :
MD Medical School, Padjadjaran University, Bandung, Indonesia
Internal Med Medical School, Padjadjaran University, Bandung, Indonesia
Pulmonology Consultant Collegiums of Internal Medicine, Indonesia
MSc Medical School, Padjadjaran University, Bandung ,Indonesia
PhD Medical School, Padjadjaran University, Bandung , Indonesia

Occupation :
Staf of Respirology Division & Critical Care Internal Medicine, Faculty of Medicine Padjadjaran
university/Hasan Sadikin General Hospital, Indonesia
Coordinator of MDR-TB Team Hasan Sadikin General Hospital Bandung, Indonesia

Organization :
Society of Internal Medicine West Java, - Indonesia
Society of Respirologi Indonesia (PERPARI)
Fellow American College of Chest Physcian (ACCP)
Member European Respiratory Society (ERS)
Diagnostic Approach of TB
Prayudi Santoso
Internal Medicine Department, Division of Pulmonary and Critical Care,
Hasan Sadikin Hospital,
University of Padjadjaran Medical School
Bandung Indonesia
2018
prayudimartha@yahoo.com
TB is a difficult disease?

 Diagnostic ?

 Therapeutic ?

 Adherence ?
Diagnosis of TB
 Clinical evaluation
 Microbiology
 Radiology
 Tuberculin test/IGRA
 Anatomical pathology
 Non-conventional & new methods
Standards for Diagnosis ISTC
Standard 1.
To ensure early diagnosis, providers must be aware of individual
and group risk factors for tuberculosis and perform prompt
clinical evaluations and appropriate diagnostic testing for
persons with symptoms and findings consistent with tuberculosis.
Standards for Diagnosis
Standard 2.
All patients, including children, with unexplained cough lasting
two or more weeks or with unexplained findings suggestive of
tuberculosis on chest radiographs should be evaluated for
tuberculosis.
Standards for Diagnosis
Standard 3.
All patients, including children, who are suspected of having
pulmonary tuberculosis and are capable of producing sputum
should have at least two sputum specimens submitted for smear
microscopy or a single sputum specimen for Xpert® MTB/RIF*
testing in a quality-assured laboratory. Patients at risk for drug
resistance, who have HIV risks, or who are seriously ill, should
have Xpert MTB/RIF performed as the initial diagnostic test.
Blood-based serologic tests and interferon-gamma release
assays should not be used for diagnosis of active tuberculosis.
The diagnosis of the patient with MDR-TB
must start with the identification of the
presumptive to have resistance, and the
grade of the presumptive , and then
laboratory diagnostic to confirm the
diagnosis
Presumptive TB MDR
(Indonesia Ministry of Health )
1. Chronic TB cases
2. Patients who not conversion in cat.2
3. Patients who had been treated wtih second line drug (Non
DOTS Programe)
4. Failure to the standard short course of therapy cat. I
5. Patients who remain smear + at 2-3 month of the category 1
6. TB relapses
7. Return after treatment to loss follow up cat .1 and or or cat. 2
8. Exposure to a known MDR TB- case
9. TB-HIV
Clinical Manifestations of TB
Depends on location
 Any organ or tissue may be affected

 Pulmonary

 Pleural, lymphatic, genitourinary, osteoarticular,


meningeal
 Disseminated: more common in AIDS and other
immunodeficiencies

Symptoms: same in DS-TB and DR-TB


Clinical Manifestations of TB
 The clinical and/or X-ray NOT improving during
treatment: may suggest MDR TB

 Never accept MDR-TB diagnosis based ONLY on


clinical and radiologial criteria.

MDR-TB is a laboratory diagnosis


Diagnosis of TB
 Clinical evaluation
 Microbiology
 Radiology
 Tuberculin test/IGRA
 Anatomical pathology
 Non-conventional & new methods
Conventional Laboratory
Procedures
 Smear microscopy

 Culture

 Species identification

 Drug susceptibility tests


Direct Smear Microscopy:
sensitivity and specificity
 > 10000 bacilli/ml sputum are required for positive result
 Low sensitivity

Very Important
 To obtain good sample

Same for DS-TB and DR-TB


Conventional Laboratory
Procedures
 Smear microscopy

 Culture

 Species identification

 Drug susceptibility tests


Mycobacterial Culture
Advantages
 The only test that confirm definite TB

 More sensitive (detects 10 bacilli/mL sputum)

Disadvantages
 Very slow growth (3–8 weeks)

 Less accessible than microscopy

 More expensive than microscopy

Pivotal in the diagnosis and follow-up of MDR TB


Microbiology Methods
for Identification of species

 Phenotypic methods
 Growth characteristics: growth time, morphology of
colony, pigment production

 Genotypic methods (DNA probes)


 Technique is faster
 Differentiates M.tb complex from MOTT
Diagnosis of TB
 Clinical evaluation
 Microbiology
 Radiology
 Tuberculin test/IGRA
 Anatomical pathology
 Non-conventional & new methods
Radiological Manifestations of TB

 In diagnosis
 Very easy and of great value in suspected diagnosis
 Non specific: all X-ray patterns can be found in other
diseases

 In prognosis and respons to treatment, it is not


definitive

No Differences with DR TB and DS TB


Diagnosis of TB
 Clinical evaluation
 Microbiology
 Radiology
 Tuberculin test/IGRA
 Anatomical pathology
 Non-conventional & new methods
Diagnosis of TB disease

 PPD

 IGRA

MDR TB should be PPD+/IGRA +  little value 


not indicated
Diagnosis of TB
 Clinical evaluation
 Microbiology
 Radiology
 Tuberculin test
 Anatomical pathology
 Non-conventional & new methods
Pathology in Diagnosis of TB
 In cases when bacteriology in negative.
 Specially in extra pulmonary TB cases
 Suggestive pathology (necrotizing granuloma, datia
langhans) may help in diagnosis
 Pathology same in DS and DR-TB
Conventional versus newer methods for
detection of drug resistance

 Classical microbiological methods


 Well established
 Cumbersome

 Time consuming

 Newer methods
 Rapid
Rapid or Molecular DST
 Detects the genetic mutation in the TB which that responsible
for or associated with the resistance.

• In addition to detection of resistance mutations, can also


simultaneously detect and identify M. tuberculosis in the
sputum specimen.

• Examples include GeneXpert® System (Xpert MTB/RIF,


Cepheid, USA), GenoType® MTBDRplus and MTBDRsl
assays (Hain Lifescience GmbH, Germany), and INNO-Li-
PA Rif.TB line probe assay (Innogenetics Inc., Belgium).
Penempatan GeneXpert di Indonesia
Sumatera Barat:
RS Achmad Mochtar Jawa Tengah: Kalimantan
RS Moewardi Barat
Aceh: Riau:
RS Kariadi RS Soedarso
RS Zainoel Abidin RS Arifin Achmad RS Cilacap Sulawesi Utara
Kalimantan RS Kandou
RS Kudus
Timur
Bangka Belitung: RS Ario Wirawan Papua Barat
RS Depati RS AW Sulawesi Tengah
RS Undata RS Kabupaten Sorong
Hamzah Sjahranie
Papua
BLK Jayapura

Jambi:
RS Mattaher

Bengkulu:
RS M Yunus
Sumatera Utara:
RS Adam Malik
Sulawesi Barat:
RS Sulawesi Sulawesi Tenggara:
Lampung: Barat RS Bahtera Mas
RS Abdul Moeloek Riau Islands:
RS Embung Fatimah
Yogyakarta:
Mikrobiologi UGM
NTB: Maluku:
Sumatera Selatan:
RS NTB RS Haulussi
RS M Hoesin NTT:
DKI Jakarta: Bali: SouthRS
Sulawesi:
Jawa Barat: RS Sanglah Johann
RS Labuang Baji
RS Persahabatan
RS Hasan Sadikin Jawa Timur:
Mikrobiologi UI NHCR es
BLK Bandung RS Soetomo
RS Pengayoman
RSP Gunawan BBLK Surabaya
41 Mesin
RS Saiful Anwar GeneXpert
RS Jember
RS Soedono
Alur Diagnosis TB Paru pada orang Dewasa
Bagan 1. Algorithme TB dan TB MDR di Indonesia
Terduga TB

Pasien baru, tidak ada riwayat pengobatan TB, tidak ada riwayat kontak Pasien dengan riwayat pengobatan TB, pasien dengan riwayat
erat dengan pasien TB RO, pasien dengan HIV (-) atau tidak diketahui kontak erat dengan pasien TB RO, pasien dengan HIV (+)

Pemeriksaan Klinis dan Pemeriksaan bakteriologis dengan Mikroskop atau TCM

Tidak memiliki akses untuk TCMTB Memiliki akses untuk TCM TB

Pemeriksaan Mikroskopis BTA Pemeriksaan TCM TB


(Sewaktu dan Pagi)

MTB Pos, Rif MTB Pos, Rif MTB Neg


(- -) (+ +) Sensitive Resistance
(+ -)
Tidak bisa
dirujuk
TB Terkonfirmasi TB Terkonfirmasi TB RR Foto Toraks
Bakteriologis Bakteriologis
Foto Terapi
Toraks Antibiotika
Non OAT

Mulai Pemeriksaan Gambaran Tidak


Pengobatan Pengobatan Biakan dan Uji mendukung Mendukung
TB TB
Gambaran Tidak TB Lini 1 TB RO Kepekaan OAT
Mendukung Mendukung Lini 1 dan Lini 2
TB TB

Ada Tidak Ada Perbaikan TB RR TB MDR TB Pre XDR TB XDR


Perbaikan Klinis, ada factor
Klinis risiko TB, dan atas
pertimbangan
dokter Lanjutkan Pengobatan TB RO TB Klinis
Pengobatan TB RO dengan Paduan Baru
TB Klinis Bukan TB
TB Klinis
Pengobatan
TB Lini 1
Cari kemungkinan
Pengobatan
penyebab penyakit lain
TB Lini 1
Problems in the diagnosis of TB

Direct detection
by molecular
assay Molecular assays are rapid, specific
and can detect few genome copies per samples
DST nowadays: molecular

Xpert MTB/RIF Whole Genome


Sensitivity -89% Sequencing
Specificity – 99% Sensitivity -96.5%
Specificity – 99.7%
Penemuan kasus TB

Penemuan pasif TB: Penemuan Aktif TB:


 Delayed diagnosis • Prompt diagnosis
 Missed diagnosis • Prompt treatment
 Delayed treatment • Memperbaiki health
VS outcome
 Penularan meningkat
• Memutus rantai
penularan
Conclusion
Based on diagnostic for TB patients are history
taking and laboratory

The diagnosis of the patient with MDR-TB must start


with the identification of the presumptive to have
resistance, and the grade of the presumptive , and
then laboratory diagnostic to confirm the diagnosis
HASAN SADIKIN GENERAL HOSPITAL

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