SoedarsonoSoedarsonoBagianBagian PenyakitPenyakit ParuParu

F.K F.K UnairUnair--RSU dr. RSU dr. SoetomoSoetomo

Low-incidence, high income

area

Low-incidence, high income

area

High-incidence, low income

area

High-incidence, low income

area

- Diagnostic approach - Methods of patient

supervision

- Monitoring for response

-Treatment regimens

Histopatholo-gical test

Epidemiologic approach

Imaging technique

Microbiological test

Clinical assesment

Diagnosis Diagnosis of TB of TB

GejalaGejala KlinisKlinisInsidious Insidious

Not alarmingNot alarming

BatukBatuk lama lama ((≥≥ 3 3 mingguminggu))

SuspekSuspek TBTB

PemeriksaanPemeriksaan fisisfisis

• Kurang spesifik

• Sangat kecilmemberikontribusidiagnosis TB

Pemeriksaan radiologis

Tidak ada tanda radiologis yang patognomonis TB (paru / ekstra paru)Gambaran yang mengarah TB merupakanindikasi perlunya evaluasi mikrobiologis.Sangat sensitif namum tidak spesifikFoto toraks dapat tampak normal :

TB primerPenyakit masih sangat awalPasien HIV yang imunokompromais

Results of radiographic examination compared with those of sputum smear microscopy (S) and sputum culture (C) in outpatients with clinical signs suggestive of tuberculosis

205215321302229Total

1680108-1698Normal

291148304Other abnormal shadows (non-TB)

81420122227Tuberculosis (TB)

C -C -C +C +

S -S +S -S +

Result of sputum examinationNo. of

patientsClassification by

radiography

The Tuberculosis Association of India / IUATLD, 1975

Laki 36 th : infiltrat dengan kavitas dikedua lobus superior dg retraksi

struktur di daerah tsb. Diagnosis TB dikonfirmasi dengan hapusan

mikroskopis dan kultur.

Laki 72 th : diagnosis TB paru berdasarkangambaran radiologis, pd kenyataannya

pasien tidak menderita TB aktif(TB sisa/inaktif)

Wanita 42 th : adenopati hilus kanandan infiltrasi parahiler diagnosis TB

dikonfirmasi dengan kultur

Bayi laki 7 bulan : massaadenopatimediastinal besar yg

menyebabkkan kolaps lobus kiri atas. Diagnosis TB ditegakkan dg pem

histopatologi dan kultur spesimen biopsi

Laki 49 th : tampak nodul ireguler batastidak tegas di lob kanan atas. Awalnyadidiagnosis Ca bronkogenik, ternyatahasil kultur menegakkan diagnosis TB

Foto menunjukkan massa yang besar dilob sup kanan. Dugaan klinis tumor paru,

pemeriksaan patologi dan kultur biopsitransbronkial menegakkan diagnosis TB

PemeriksaanPemeriksaan HistopatologiHistopatologi

•• HapusanHapusan mikroskopismikroskopisnegatifnegatif

•• PenyebaranPenyebaran hematogenhematogen•• TB TB ekstraekstra paruparu•• SuspekSuspek malignansimalignansi

BiopsiBiopsi untukuntuk pempemhistopatologihistopatologidiperlukandiperlukan untukuntukidentifikasiidentifikasigranulomagranuloma kaseosakaseosa& KULTUR !& KULTUR !

PemPem. . mikrobiologismikrobiologisHapusanHapusan langsunglangsung

identifikasiidentifikasi BTA :BTA :

SederhanaSederhana & & reprodusibelreprodusibelCepatCepatMurahMurahSpecifitiSpecifiti tinggitinggiDapatDapat menilaimenilai drajatdrajatpenularanpenularan

Untuk meningkatkan sensitiviti pem BTA 3 x

TesTes diagnostikdiagnostik yang ideal:yang ideal:

SederhanaSederhana & & reprodusibelreprodusibelCepatCepatMurahMurahsensitivitisensitiviti dandan specifitispecifiti tinggitinggiDapatDapat menilaimenilai drajatdrajat penularanpenularan

TehnikTehnik yang yang mudahmudah & & reprodusibelreprodusibel, , cepatcepat, , murahmurah

Tes diagnostik yang sangat ideal :

Idem sebelumnya, ditambah kriteria : Tidak dibutuhkan keahlian & sampelyang berlebihanDapat memberikan data resistensiDapat membedakan infeksi TB latendan TB aktifDapat menilai respons terapiDapat membedakan M.tb dg MOTT

KulturKulturStandarStandar emasemas untukuntukdiagnosisdiagnosisFollowFollow--upupKonfirmasiKonfirmasi kesembuhankesembuhan

IndikasiIndikasi kulturkultur tgttgt padapada ::EndemitasEndemitas penyakitpenyakitInfrastrukturInfrastruktur kesehatankesehatandaerahdaerah setempatsetempat

ALL PULMONARY TB SUSPECTS

Sputum AFB Microscopy

Two or three smears positive

Only one smear positive

Three smears negative

X-ray and medical officer’s

judgment Repeat AFBNo Improvement

Improved

One or more smears positive

All smears negative

X-ray and medical officer’s judgment

No TBYes TB

Non-anti TB antibiotics

WHO (2003) : Treatment of TB Guidelines for National Programmes

PendekatanPendekatan penderitapenderita suspeksuspek TB TB paruparupadapada kunjungankunjungan medismedis pertamapertama

* Tergantung pada fasiliti dan SDM yang ada : bila terbatas bisa langsungtreatment (NTP), bila memungkinkan pegambilan spesimen (invasive, misbronkoskopi, biopsi dll) sebelum terapi dimulai

PendekatanPendekatan penderitapenderita suspeksuspek TB TB paruparu padapadakunjungankunjungan medismedis keduakedua ((apabilaapabila pxpx masihmasih batukbatuk) )

InduksiInduksi sputumsputumSuatuSuatu metodemetode mendapatkanmendapatkan sampelsampel sputum yang sputum yang sesuaisesuai diagnosis & diagnosis & meningkatkanmeningkatkan diagnosis diagnosis dinidiniInduksiInduksi sputum (IS) sputum (IS) terbuktiterbukti efektifefektif padapada pasienpasienyang yang tidaktidak mampumampu mengeluarkanmengeluarkan sputum sputum atauataupasienpasien dengandengan hapusanhapusan sputum BTA sputum BTA negatifnegatif..HandokoHandoko (2004) : BTA (+) (2004) : BTA (+) padapada IS dg saline 0,9% IS dg saline 0,9% lebihlebih tinggitinggi dibandingdibanding tanpatanpa IS (62,5% IS (62,5% vsvs 37,5%)37,5%)UntukUntuk negaranegara pendapatanpendapatan rendahrendah, , metodemetode iniinicukupcukup costcost--effectiveeffective

PerananPeranan BronkosokopiBronkosokopi Fiber Fiber OptikOptikAdaAda 2 2 kegunaankegunaan dalamdalamdiagnosis TB diagnosis TB

1.1. MendapatkanMendapatkan sampelsampel padapadapasienpasien yang yang tidaktidak mampumampumengeluarkanmengeluarkan sputum sputum secarasecaraspontanspontan

2.2. DiagnonisDiagnonis cepatcepat ((melaluimelaluihapusanhapusan langsunglangsung atauatauhistopatologi)padahistopatologi)pada pasienpasien--2 2 yang yang membutuhkanmembutuhkan intervensiintervensi/ / terapiterapi segerasegera, , sambilsambilmenunggumenunggu hasilhasil kulturkultur..

PerkembanganPerkembangan diagnosis diagnosis laboratorislaboratoris TB TB

BiakanMedia agar padat: - Lowenstein

Jensen (LJ) - Ogawa Perkembanganbaru Media cair : - MGIT

- Middlebrooklebih cepat(BACTEC)

Bakteriologimolekuler :

Uji PCR Uji LCR

Serologi :

Uji ELISA-TB, ujiMyco-dot, uji PAP -TB, uji TB-Dot (Dot-EIA)

Ujiimunokromatografi(Uji ICT)

RESUME

DIAGNOSTIK

LABORATORIS-TB

RESUME

DIAGNOSTIK

LABORATORIS-TB

Sputum BTA 3 X : - uji saring terdepan, murah, praktis, sens >

- pemantauan hasil tx

Biakan dahak : - STANDARD EMAS - uji resistensi- pemantauan hasil tx

Uji PCR / LCR : - unt. kasus bermasalah- uji resistensi cepat

Uji Serologi : - pilihan utama untuk

PAUCIBACILLARYTB

Rangkuman diagnosis TB

1. Pasti : kultur sampel (+), dg identifikasi M.tb2. Sangat mungkin : sebagai dasar untuk memulai

terapi dan mencatatnya sebagai kasus TB menurut kerangka kerja NTP :

Hapusan mikroskopis (+) ( tidak perlu kultur)Nekrosis kaseosa (+) pada pem histopatologi (harus dikultur)

3. EksklusiBerdasarkan kriteria klinis, radiologis & laboratorisSampel harus selalu diproses untuk pem hapusanmikroskopis dan kultur

Peranan provider dalam prinsip dasarterapi TB‘Evidence-based ratings’ opsi terapi TBStrategi ‘patient-centered care’Monitoring respons terapi melaluipemeriksaan mikroskopisIndikasi uji resistensiRekomendasi WHO/IUATLD untukmenerapkan strategi DOTS dlm kontrol TB di negara2 insidens tinggi-income rendah

BEBERAPA ASPEK YANG DITEKANKANDALAM TERAPI TB SAAT KINI, a.l :

TANGGUNG JAWABTANGGUNG JAWAB

PENDEKATANPENDEKATAN

Pemberian regimen yg‘appropriate’ + adekuat

& menjamin kelengkapan

minum obat

Direct Observe Therapy (DOT)

PRINSIP DASAR TERAPI TB–PERANAN PROVIDER

IDSA/USPHS* Rating System for IDSA/USPHS* Rating System for Treatment RecommendationsTreatment Recommendations

A.A. Preferred; should Preferred; should generally be offeredgenerally be offered

B.B. Alternative; acceptable Alternative; acceptable to offerto offer

C.C. Offer when preferred/Offer when preferred/alternative regimens alternative regimens cannot be givencannot be given

D.D. Should generally not Should generally not be offeredbe offered

E.E. Should never be offeredShould never be offered

I.I. At least one properly At least one properly randomized trial with randomized trial with clinical endpointsclinical endpoints

II.II. Clinical trials that Clinical trials that either are not either are not randomized or were randomized or were conducted in other conducted in other populationspopulations

III.III. Expert opinionExpert opinion

Strength of the Recommendation Quality of Supporting Evidence

* IDSA-Infectious Diseases Society of America; USPHS-U.S. Public Health Service

Treatment of CultureTreatment of Culture--Positive TB (1)Positive TB (1)

Initial Phase

Continuation Phase

* Continuation phase increased to 7 months if initial chest x-ray shows cavitationand specimen collected at end of initial phase (2 months) is culture positive

(Rated: AI in HIV-negative, AII in HIV-positive patients)

2 months- INH, RIF, PZA, EMB daily (56 doses, within 8 weeks)

Options:1) 4 months - INH, RIF daily (126 doses, within 18 weeks)2) 4 months - INH, RIF twice / week (36 doses, within 18 weeks)3) 7 months - INH, RIF daily (217 doses, within 31 weeks)*4) 7 months - INH, RIF twice / week (62 doses, within 31

weeks)*

* Regimen rated BII for HIV-positive patients with CD4+ T-lymphocytes cell count >100/µl. Not recommended for those with CD4+ T-lymphocytes cell count < 100/µl

Continuation Phase

Treatment of CultureTreatment of Culture--Positive TB (2)Positive TB (2)Twice-Weekly Options

(Rated: AII for HIV-negative, BII for HIV-positive patients*)

0.5 months - INH, RIF, PZA, EMB daily (10-14 doses, within 2 weeks)THEN1.5 months - INH, RIF, PZA, EMB twice / week (12 doses, within 6 weeks)

Options:1) 4 months - INH, RIF twice / week (36 doses, within 18 weeks)2) 7 months - INH, RIF twice / week (62 doses, within 31 weeks)

Initial Phase

Continuation Phase

Treatment of CultureTreatment of Culture--Positive TB (3)Positive TB (3)Thrice-Weekly Options

(Rated: BI for HIV-negative, BII for HIV-positive patients)

Initial Phase

2 months - INH, RIF, PZA, EMB 3 times / week (24 doses, within 8 weeks)

Options:1) 4 months - INH, RIF 3 times / week (54 doses, within 18

weeks)2) 7 months - INH, RIF 3 times / week (93 doses, within 31

weeks)

* Twice weekly dosing is not recommended for persons with CD4+ T-lymphocytes cell count < 100/µl

Treatment of CultureTreatment of Culture--Positive TB (4)Positive TB (4)Regimens without Pyrazinamide

(Rated: CI for HIV-negative, CII for HIV-positive patients)

Continuation Phase

2 months - INH, RIF, EMB daily (56 doses, within 8 weeks)Initial Phase

Options:1) 7 months - INH, RIF daily (217 doses, within 31 weeks)2) 7 months - INH, RIF twice / week (62 doses, within 31

weeks)*

RECOMMENDED TREATMENT REGIMENS FOR EACH DIAGNOSTIC CATEGORY RECOMMENDED TREATMENT REGIMENS FOR EACH DIAGNOSTIC CATEGORY (WHO 2003)(WHO 2003)

TB TREATMENT REGIMENSTB TREATMENT REGIMENS

TB PATIENTSTB PATIENTSTB TB

DIAGNOSTIC DIAGNOSTIC

CATEGORYCATEGORY

Specially designed standardized or Specially designed standardized or individualized regimens are suggested for individualized regimens are suggested for

this categorythis category

Chronic and MDRChronic and MDR--TB cases TB cases ( still sputum( still sputum--positive after positive after supervised resupervised re--treatment)treatment)

IVIV

4 HR 4 HR or or

6 HE daily6 HE daily2 HRZE2 HRZE

New smearNew smear--negative PTB negative PTB (other than in (other than in CategotrCategotr I); I); Less severe forms of EPTBLess severe forms of EPTB

IIIIII

5 HRE5 HRE2 HRZES/ 2 HRZES/ 1 HRZE1 HRZE

Previously treated sputum Previously treated sputum smearsmear--positive PTB : positive PTB : -- relapse; relapse; -- treatment after interruption; treatment after interruption; -- treatment treatment failurefailuredd

IIII

4 HR 4 HR or or

6 HE daily6 HE daily2 HRZE2 HRZE

New smearNew smear--positive patients; positive patients; New smearNew smear--negative PTB w/ negative PTB w/ extensive extensive parenchymalparenchymalinvolvement; involvement; Severe concomitant HIV Severe concomitant HIV disease or severe forms of disease or severe forms of EPTBEPTB

II

CONTINUATION PHASE CONTINUATION PHASE (DAILY OR 3 TIMES (DAILY OR 3 TIMES

WEEKLY)WEEKLY)

INITIAL PHASE INITIAL PHASE (DAILY OR 3 TIMES (DAILY OR 3 TIMES

WEEKLY)WEEKLY)

PATIENT-CENTERED CARE

CLINICAL

SOCIAL CIRCUMSTANCES

Private SectorPublic Health Departments

Private SectorPublic Health Departments

DOTDOT

M1 M2 M5 M6

WHEN TO MONITOR SPUTUM SMEAR ?

At time of diagnosis

At end initial phase

In continuation phase

On complete of treatment

6 month treatment regimen

TAI TREATMENT FAILURE

NEW CASE

RELAPS FAILURE OF RETREATMENT / CHRONIC CASE

PR AR AR

AR AR

MDR

m1 m2 m3 m4 m5 m6

m1 m2 m3 m4 m5 m6 m7 m8

1st course chemotherapy

2nd course chemotherapy

PR = primary resistance ;AR = Acquired Resistance; MDR = Multi-Drug Resistance

KAPAN PERLU DILAKUKAN UJI RESISTENSI ?

RekomendasiATS/CDC/IDSA vs WHO / IUATLD

Rekomendasi ATS/CDC/IDSA tidak harusdiasumsikan dapat diimplementasikandisemua keadaan/kondisi epidemiologi & ekonomiBesarnya insidens TB dan sumber daya disuatu area sangat menentukan pendekatantatalaksana TB yang dipilih.

Target WHO / IUATLD : negara-negaradimana kultur, uji kepekaan & pemradiologis tidak tersedia merata /luas.

Rekomendasi WHO / IUATLD : Strategidalam kontrol TB adalah “DOTS” (Directly Observed Treatment, Short Course).

RekomendasiATS/CDC/IDSA vs WHO / IUATLD 2

FIVE COMPONENTS OF DOTSFIVE COMPONENTS OF DOTS

1.1. Government COMMITMENT to sustained TB control Government COMMITMENT to sustained TB control activitiesactivities

2.2. Case detection by SPUTUM SMEAR MICROSCOPY Case detection by SPUTUM SMEAR MICROSCOPY among symptomatic patientsamong symptomatic patients

3.3. STANDARDIZED TREATMENT regimen of 6STANDARDIZED TREATMENT regimen of 6--8 months, 8 months, with DOT for at least the initial 2 monthswith DOT for at least the initial 2 months

4.4. A regular, uninterrupted SUPPLY OF ALL ESSENTIAL A regular, uninterrupted SUPPLY OF ALL ESSENTIAL ANTI TB DRUGSANTI TB DRUGS

5.5. A STANDARD RECORDING & REPORTING system that A STANDARD RECORDING & REPORTING system that allows assessment of treatment results for each allows assessment of treatment results for each patient & of the TB control program overallpatient & of the TB control program overall

KOMITMEN (DOKTER) KOMITMEN (DOKTER)

DIAGNOSIS UTAMA TB : IDENTIFIKASI KUMAN (BTA) VIA

HAPUSAN DAHAK LANGSUNG

DIAGNOSIS UTAMA TB : IDENTIFIKASI KUMAN (BTA) VIA

HAPUSAN DAHAK LANGSUNG

KETERSEDIAAN OBATKETERSEDIAAN OBAT

PENGOBATAN JANGKA PENDEK & PENGAWASAN LANGSUNG

PENGOBATAN JANGKA PENDEK & PENGAWASAN LANGSUNG

PENCATATAN & PELAPORAN YANG BAKU

PENCATATAN & PELAPORAN YANG BAKU

1

2

3

4

5

AGENDA RESEARCH PENGOBATAN TB (1)

Obat anti TB baru, diperlukan karena 3 alasan :1. Menyederhanakan atau memperpendek lama

pengobatan TB khususnya untuk kasus yang kuman masih sensitif terhadap obat

2. Menyempurnakan pengobatan penderita MDR-TB

3. Pengobatan infeksi TB laten yang lebih efektifdan efisien

Newer Anti-TB drugs• Rifabutin: For patients receiving medications having

unacceptable interactions with rifampin (e.g., persons with HIV/AIDS)

• Rifapentine: Used in once-weekly continuation phase for HIV-negative adults with drug-susceptible noncavitary TB and negative AFB smears at completion of initial phase of treatment

• New fluoroquinolone (levofloxacin, gatifloxacin, moxifloxacin)

• Nitroimidazopyrans• Linezolid

AGENDA RESEARCH PENGOBATAN TB (2)

• Intervensi lain untuk menyempurnaknefikasi pengobatan

• Alternafif metode cara pemberian obat & metode imunodulasi dan imunoterapi

Metode yang lebih baik dalammengidentifikasi & me ‘manage ‘kasus-kasus dengan risiko tinggiFasilitasi penelitian tentang pemberianpengobatan dan penyempurnaan outcome

RangkumanRangkuman pendekatanpendekatan tatalaksanatatalaksana TB TB berdasarkanberdasarkan WHO/IUATLD & ATS/CDC/IDSA WHO/IUATLD & ATS/CDC/IDSA (1)(1)

Evaluasi data awal fungsi organsebelum pengobatan, rutindilakukan pada semua kasus TB

Evaluasi data awal fungsi organsebelum pengobatan tidak harusdilakukan

Uji kepekaan terhadap OAT padaawal pengobatan seharusnyadilakukan pada semua kasus TB

Uji kepekaan terhadap OAT sebelum pengobatan tidakdianjurkan untuk semua kasus TB

Foto toraks merupakan salah satusarana diagnosis rutin untuk semuakasus TB

Foto toraks direkomendasikanhanya untuk pasien dengan sputum BTA negatif

Diagnosis, klasifikasi & penilaianrespons terapi lebih didasarkan ataspemeriksaan KULTUR M.tb

Diagnosis, klasifikasi & penilaianrespons terapi didasarkan ataspemeriksan SPUTUM BTA

ATS/CDC/IDSAWHO/IUATLD

RangkumanRangkuman pendekatanpendekatan tatalaksanatatalaksana TB TB berdasarkanberdasarkan WHO/IUATLD & ATS/CDC/IDSA WHO/IUATLD & ATS/CDC/IDSA (2)(2)

Batasan pengobatan lengkap : lebih didasarkan jumlah dosis obatyang telah diminum

Batasan pengobatan lengkap : lebih didasarkan atas lama/waktusiklus pengobatan yang telah dijalani

Ada beberapa opsi regimen ygdidasarkan kekuatan rekomendasidan hasil uji klinis sebelumnya

Regimen ditentukan berdasarkanhasil pem. BTA, riwayatpengobatan sebelumnya, beratpenyakit kategori I,II, III, IV

Monitoring pemeriksaan BTA & kultur dilakukan tiap bulan sampai 2 kali pemeriksaan ber turut2 negatif

Monitoring pemeriksaan BTA dilakukan akhir bulan ke 2, 5 dan 6pengobatan

ATS/CDC/IDSAWHO/IUATLD

Pada akhir siklus pengobatan : adakemungkinan diperpanjang 3 bulanlagi untuk kasus2 tertentu

Pada akhir siklus pengobatan : biladinyatakan gagal mulai lagipengobatan dengan kategori II

Batasan relaps : pasien kembalikulturnya positif atau klinis & radiologis menunjukan tanda2 aktif

Batasan relaps : pasien kembaliBTA nya positif setelah dinyatakansembuh / pengobatan lengkap

Batasan gagal pengobatan : didasarkan hasil kultur yg positifpada akhir bulan ke 4 pengobatan

Batasan gagal pengobatan : didasarkan hasil pemeriksaan BTA dua kali ber-turut2 positif padaakhir pengobatan

ATS/CDC/IDSAWHO/IUATLD

RangkumanRangkuman pendekatanpendekatan tatalaksanatatalaksana TB TB berdasarkanberdasarkanWHO/IUATLD & ATS/CDC/IDSA WHO/IUATLD & ATS/CDC/IDSA (3)(3)