Diagnosis , Terapi & Vaksin TB

Tjandra Yoga Aditama

Selamat
Siang
BTA = Basil Tahan Asam
 Pemeriksaan baru
BD ProbeTec ET
Genotypic marker IS6110
Culture based AST – 4 – 6 minggu

BACTEC – MGIT – ESP Myco –

E-test – FASTplaqueTB- Luciferase Test

MABA-LRP & Bioluminescence assay-MODS-

DNA sequencing-PCR, LIPA, DNA Micro assays

Finger printing (sidik jari) RFLP
Perkembangan Terapi
Kategorisasi Pengobatan
• Kategori I - 2 RHZE / 4 R3H3
baru , BTA(+), BTA(-) berat
• Kategori II - 2RHZES/ RHZE/
5R3H3E3
gagal, kambuh
• Kategori III - 2 RHZ / 4 R3H3
BTA(-) Ro(+)

Pendekatan “Baru” :
• FDC
• Menggabungkan Kategori I & III
FDC, jaminan bioavailability – tergabung jadi “satu”
Objectives for TB drug development
 Shorten the total duration of
effective treatment and/or significantly
reduce the total number of doses
needed to be taken under DOTS
supervision
 Improve the treatment of MDR-TB
 Provide a more effective treatment of
latent TB

Tuberculosis 81 (2001), Supplement 1

‘Scientific Blueprint for TB Drug Development’
Penemuan Obat Baru
 Drug Development Pipeline

Gap
Basic Phase Registration
Pre- Phase Phase
Research Discovery III & Post
Clinical I II Clinical
 Drug Development Outsourcing Network

Under Evaluation:
Peru
Russia
India
South Africa Existing Sites
Brazil
 0
2
4
6
8
10
12
B
as
ic
R
es
ea
rc
h
D
is
co
ve
r y
Le
ad
Id
en
tif
ic
at
io
Le n
ad
O
pt
im
iz
at
io
n
(by project)

Pr
ec
l in
ic
al

Cl
in
ic
al
Mapping Results to Date
 WG Portfolio Data
Lead Lead
Pre-Clinical Clinical
Identification Optimization

PA-824
Pyridones Analogs PA824 Moxifloxacin
and Quinolizines
Thiolactomycin
LL-3858
Ascididemin Rifapentine
Compounds

(Pyrroles)
Compounds
KRQ 10018

Third Generation Rifabutin

Macrolides PA 20013

Ethambutol Capreomycin
Analogs

Gatifloxacin
MJH 98-I-81
& Analogs

Rifalazil Levofloxacin
Analogs

Anti-Persisters Linezolid

Ofloxacin

Non-profit Project Industry

TB Project
Alliance Project Combination Project
 PA-824
“[This] deal tells me … that biotech leaders,
international health officials and philanthropic
O2N groups are trying to create mechanisms to
address needs that would otherwise fall through
N the cracks. I’m keeping my fingers crossed,
both for the TB drug and the larger experiment
in non-profit drug development.”
N O
Tom Abate, Biotech columnist,
San Francisco Chronicle.

F
O O F
F
 TBTC Studies
• Treatment trials
– Rifapentine: Phase II and III studies completed, LTBI
study enrolling
– Rifabutin in TB/HIV: enrollment suspended
– INH resistance/intolerance: enrolling
– Moxifloxacin: Phase II enrolling
• Laboratory studies – Animal studies
– Serum banking project
– NAA/surrogate markers
• Pharmacokinetic studies
Percobaan “Binatang”
 SATBTrials – Planned
Studies

• Comparative EBA study of moxi, gati, oflo

(in collaboration with TRC)
• Phase III trial of gatifloxaxin to shorten
treatment (one site under EDCTP)
• Studies of surrogate markers
• Evaluation of aerosolize drug delivery
• Network-wide RCT under discussion
 1st Results from MXF Studies
Lung CFU counts

10
Log CFU in entire lung
9
8
7 Untreated
6 2RHZ+4RH
2RHZM+4RHM
5 2RHM+4RH
4 2RMZ+4RM
3 2MHZ+4MH
2
1
0
0 1 2 3 4 5 6
Duration of treatment (mos.)

Moxifloxacin Murine Model Results of log10 CFU counts from lung homogenates. (Jacques
Grosset & William Bishai - JHU)
TB&HIV
Main interventions to interrupt the sequence of events by which HIV fuels TB

Transmission of infection
M. tuberculosis
infection

Condoms TB
HIV Recurrence preventive
infection STI treatment after treatment treatment
BCG Safe IDU
Rifampicin
Inadequate containing
M. tuberculosis treatment regimens
infected person
 Intensified
HAART Untreated case-finding
 Decreased
diagnostic &
treatment delays

TB progression
Active TB
TB reactivation

TB preventive treatment
Perkembangan Vaksin
vaccinate Infants

vaccinate
Adolescents

Acute Highly
Infection infectious

Latent Reactivation in
Infection Adolescents
and Adults
vaccinate Infants

vaccinate
Adolescents

Acute Highly
Infection infectious

Latent Reactivation in
Infection Adolescents
& Adults
 Vaccine Strategy
• To bring the best current vaccine
candidates forward as fast as possible
• To insure manufacturing and supply at an
affordable price
• To eliminate delay between licensure and
availability through early factory
construction

• Every year lost costs 2 million lives

 Rationale for TB vaccine potential
• Human immunology – Humans with
IL-12 and INF γ pathway defects
highly susceptible to TB
• Animal models that mimic human
TB can be protected with vaccines
• 20 yrs of iterative testing of
antigens that healthy infected
humans respond to have narrowed
the choices
Kandidat Vaksin
Prime Boost Strategy
For Protection against Acute
Infection and Disease in Infants

Candidates for the Priming of

Newborns:
- BCG
- Recombinant BCG
- Live attenuated recombinant
TB variant
 Candidates for Boosting Infants
and adolescents
• Recombinant fusion protein in
adjuvant
• Vectored vaccines
– MVA recombinant
– Adenovirus recombinant
– oral shigella auxotroph dsRNA
expression system
• Heat shock associated proteins
Jadi kapan dong… ?
 Summary vaccine
• A moderately effective vaccine + drug
control could eliminate the epidemic
• Based on 20 years of research a prime
boost vaccine strategy has great potential
• This new vaccine regimen could
be licensed and available in 7-10
years
• A new vaccine to prevent
reactivation possible in 10-12
years
Bagaimana sih TB di Indonesia ?
It can be done—
Achieved and sustained in
6 countries for four years!
100 Malta
Maldives
TARGET ZONE
Treatment success (%)

Cambodia
Tonga Viet Nam
Solomon Is
Cuba
Peru
Fiji
Tunisia
Bosnia & Hezegovina Morocco
Hong Kong Samoa Qata
85 Uruguay
Oma
Mongolia Marshall IsNicaragua r n
Kyrgyzstan Chile
St Lucia Morocco
Kazakhstan
80 Venezuela
Guatemala
Kenya El Salvador Djibouti
Slovenia
Sri Lanka French Polynesia
Tanzania South Africa
Turks & Caicos Is
Italy LebanonPortugal USA
Latvia
70 DR Congo
50 60 70 80 90 100 110 120
DOTS detection rate (%)
24 March 2004
 It can be done
in your country
100
100
China
Cambodia
TARGET ZONE
90 Viet Nam
Indonesia
Treatment success (%)

Afghanistan India Philippines Peru

T re a tm e n t s u c c e s s (% )

85 % Kenya Myanmar
Bangladesh Tanzania
80 90 Nigeria
Pakistan DRCongo
Ethiopia Thailand
Mozambique
70 Brazil
Zimbabwe
Russia
South Africa
60 80 Uganda

50

40 70
0 50 6020 70 80 90 100 110 120 100
10 30 40 50 60
70
70
% 80 90

DOTS detection
DOTS detection rate (%)
rate (% )

24 March 2004
Peran Serta Aktif Banyak Pihak
• Asosiasi RS Paru di Indonesia
• Penelitian TB & HIV ( IHVCB)
• Pedoman penanganan TB di tempat
kerja ( IDKI & Pus Kes Kerja )
• Pedoman Pelayanan Penyakit Paru
(DirJen YanMed)
• Pedoman Diagnosis & Terapi TB
(PDPI)
• Penelitian – penelitian TB di
Universitas
Obat & Diagnosis Baru –
Sekarang Waktunya !!

+ +
Develop new tools

To defeat the mutable TB microbe,

we must upscale efforts to develop:
 New diagnostics: FIND, TDR,
 New TB drugs: Global Alliance, Novartis
Institute, Glaxo Welcome
 New vaccines: Aeras

24 March 2004
Working Group Coordination

Treatment Today Treatment Tomorrow

DOTS-Plus New
MDR-TB TB Vaccines

HIV/TB
DOTS New TB New
Expansion TB Diagnostics
Drugs
 Evaluasi Keadaan Kini
WHA 2005 world targets:
 one at reach (cure rate 82% vs 85%)
 one uncertain (detection rate 37% vs 70%)

Yang masih harus dilakukan

Lakukan ekspansi DOTS
Jaga komitmen semua pihak
(GERDUNAS)
Penelitian menemukan obat , alat
diagnostik dan vaksin baru
Mungkinkah Indonesia jadi salah
satu penghasil teknologi baru, bukan
pengguna saja ?
Let us not fail

“We don’t need more

promises; we need to deliver
on those already made.”

- MDGs High-Level Forum,

January 2004

24 March 2004
Pantang Menyerah
TERIMAKASIH